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Find video protocols related to scientific articles indexed in Pubmed.
PTCH1 mutation is a frequent event in oesophageal basaloid squamous cell carcinoma.
Mutagenesis
PUBLISHED: 11-15-2014
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Basaloid squamous cell carcinoma (BSCC) is a rare and poorly differentiated variant of typical squamous cell carcinoma, and is characterised in part by activation of the Wnt signalling pathway. We previously demonstrated that constitutive activation of the Wnt signalling pathway by epigenetic silencing of secreted frizzled-related protein 4 (SFRP4) is observed in this tumour. Increasing evidence shows that the Wnt signalling pathway cross-talks with other developmental pathways, including the Hedgehog (HH) pathway. The HH pathway is stimulated by inactivating mutations of PTCH1, which have a well-described oncogenic role in basal cell carcinoma (BCC) of the skin. We employed polymerase chain reaction followed by direct sequencing to detect inactivating mutations of PTCH1 using archival tissue samples of 30 oesophageal BSCCs. The frequency of PTCH1 mutation was compared to that of Wnt component genes that we reported previously. We found PTCH1 mutations in 53.3% (16/30) of cases, revealing T1195S as a hotspot mutation. This frequency is quite high for cancers other than BCC of the skin, and PTCH1 mutations were almost mutually exclusive with mutations in APC, Axin1 and Axin2. Considering the fact that activation of Wnt signalling via down-regulation of APC and SFRP5 due to promoter methylation is observed in BCC of the skin, Wnt signalling activation in oesophageal BSCC might be a secondary effect of the PTCH1-inactivating mutations. These findings suggest that the HH and Wnt pathways coordinately contribute to tumourigenesis in oesophageal BSCC. Furthermore, this study provides a potential therapeutic application for HH pathway inhibitors in oesophageal BSCC with highly malignant potential.
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Case of computed tomography (CT) gastrography for the detection of multiple gastric submucosal tumors: a case report.
Nihon Shokakibyo Gakkai Zasshi
PUBLISHED: 10-07-2014
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A 66-year-old female underwent esophagogastroduodenoscopy, which revealed a 17-mm gastric submucosal tumor (SMT) located in the posterior wall of the upper area of the stomach. She was referred to our hospital for further investigation because of accumulation of radioactive substance in the gastric wall by PET-CT. CT gastrography (CTG) revealed three gastric SMTs in total. Partial gastrectomy was performed; histopathologically, they were diagnosed as gastrointestinal stromal tumor (GIST), benign schwannoma, and necrotic tissue. Gastric schwannoma is very rare, and we could find no cases with both GIST and schwannoma. Additionally, the three gastric SMTs were only detected clearly via CTG. We report on the details of this case and the usefulness of CTG for the detection of gastric SMT.
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Deeply located low-grade fibromyxoid sarcoma with FUS-CREB3L2 gene fusion in a 5-year-old boy with review of literature.
Diagn Pathol
PUBLISHED: 09-03-2014
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Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor typically affecting young to middle-aged adults. Despite its otherwise benign histologic appearance and indolent nature, it can have fully malignant behavior, and recurrence and metastasis may occur even decades later.
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Abnormality in Wnt signaling is causatively associated with oxidative stress-induced intestinal tumorigenesis in MUTYH-null mice.
Int. J. Biol. Sci.
PUBLISHED: 08-23-2014
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MUTYH is a DNA glycosylase that excises adenine paired with 8-oxoguanine to prevent mutagenesis in mammals. Biallelic germline mutations of MUTYH have been found in patients predisposed to a recessive form of familial adenomatous polyposis (MAP: MUTYH-associated polyposis). We previously reported that Mutyh-deficient mice showed a high susceptibility to spontaneous and oxidative stress-induced intestinal adenoma/carcinoma. Here, we performed mutation analysis of the tumor-associated genes including Apc, Ctnnb1, Kras and Trp53 in the intestinal tumors of Mutyh-deficient mice. In the 62 tumors, we identified 25 mutations in Apc of 18 tumors and 36 mutations in Ctnnb1 of 36 tumors. Altogether, 54 out of the 62 tumors (87.1%) had a mutation in either Apc or Ctnnb1; no tumor displayed mutations simultaneously in the both genes. Similar to MAP, 60 out of 61 mutations (98.3%) were identified as G:C to T:A transversions of which 85% occurred at either AGAA or TGAA sequences. Immunohistochemical analyses revealed the accumulation of ?-catenin in the nuclei of tumors. No mutation was found in either Kras or Trp53 in the tumors. These results indicate that the uncontrolled activation of Wnt signaling pathway is causatively associated with oxidative stress-induced intestinal tumorigenesis in the Mutyh-deficient mice.
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Histological Distinction between the Granular and Nongranular Types of Laterally Spreading Tumors of the Colorectum.
Gastroenterol Res Pract
PUBLISHED: 08-11-2014
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Colorectal laterally spreading tumors (LSTs), which are classified into granular (LST-G) and nongranular (LST-NG) types, are a good indication for endoscopic treatment. In practice, the nongranular type is more difficult to remove endoscopically than the granular type. It might be assumed that some histological differences exist between these subtypes. The objective of this study was to analyze histological features of laterally spreading tumors and compare between the granular and the nongranular types. A total of 32 cases of LSTs resected endoscopically being intramucosal tumors with no previous treatment were analyzed. The disposition of the muscularis mucosae, the vascular density, and the degree of fibrosis of the submucosal layer were determined. The outline of the muscularis mucosae in LST-NG was almost flat, but that of LST-G was wavy. The submucosal vascular density was significantly greater in the LST-NGs (61.4 ± 24.3/mm(2)) than in the LST-Gs (43 ± 22.4/mm(2); P = 0.033). There was no clear difference in the degree of submucosal fibrosis between the subtypes. A flat disposition of the muscularis mucosae and a more densely vascularized submucosal layer were characteristics of LST-NGs compared to the LST-Gs. These findings may play a role when performing the endoscopic resection of LSTs.
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GNAS mutation as an alternative mechanism of activation of the Wnt/?-catenin signaling pathway in gastric adenocarcinoma of the fundic gland type.
Hum. Pathol.
PUBLISHED: 07-01-2014
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Gastric adenocarcinoma of the fundic gland type (GAFG) is a rare variant of gastric tumor. We have recently reported the frequent accumulation of ?-catenin in GAFGs and showed that approximately half of the cases studied harbored at least 1 mutation in CTNNB1/AXINs/APC, leading to the constitutive activation of the Wnt/?-catenin pathway. However, the mechanisms of Wnt signaling activation in the remaining cases are unknown. Accumulating evidence showed that the activating mutation in GNAS promotes tumorigenesis via the activation of the Wnt/?-catenin pathway or the ERK1/2 MAPK pathway. Therefore, we analyzed the mutations in GNAS (exons 8 and 9) and in KRAS (exon 2) in 26 GAFGs. Immunohistochemistry revealed nuclear ?-catenin expression in 22 of 26 GAFGs, and 10 (38.5%) of 26 cases harbored at least 1 mutation in CTNNB1/AXINs/APC. Activating mutations in GNAS were found in 5 (19.2%) of 26 GAFGs, all of which harbored R201C mutations. Activating mutations in KRAS were found in 2 (7.7%) of 26 GAFGs, and both of these also contained GNAS activating mutations. Four of 5 cases with GNAS mutation showed nuclear ?-catenin expression, and presence of GNAS mutation was associated with ?-catenin nuclear expression (P = .01). Furthermore, 3 of these 4 cases did not harbor mutations in CTNNB1, APC, or AXINs, suggesting that mutations in the Wnt component genes and those in GNAS occur almost exclusively. These results suggest that GNAS mutation might occur in a small subset of GAFG as an alternative mechanism of activating the Wnt/?-catenin signaling pathway.
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A case of (123)I-MIBG scintigram-negative functioning pheochromocytoma: immunohistochemical and molecular analysis with review of literature.
Int J Clin Exp Pathol
PUBLISHED: 06-15-2014
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A 70-year-old Japanese woman was referred to our hospital due to hyperhidrosis and rapid weight loss of 10 kg in a month. A lump measuring 26 mm in diameter was detected in the left adrenal gland by computed tomography. Biochemical tests showed high levels of serum and urinary norepinephrine and epinephrine. However, a (123)I-MIBG scintigram failed to detect any accumulation in the left adrenal tumor. A left adrenalectomy was performed post clinical diagnosis of (123)I-MIBG negative pheochromocytoma. Microscopically, the tumor exhibited pheochromocytoma compatible features. Immunohistochemical analysis revealed low expression of VMAT1 in the tumor compared to the normal, surrounding tissue. To test for a possible genetic alteration of the monoamine transporter genes, we performed whole-exome sequencing of the VMAT1, VMAT2, and NET genes in the tumor. No significant base sequence substitution or deletion/insertion was found in any transporter. This suggests that MIBG negativity is caused by a change that is independent of the base sequence abnormalities, such as an epigenetic change. Furthermore, a retrospective literature review of (123)I-MIBG negative-scintigraphy cases indicates that a negative finding in the (123)I-MIBG scintigram is frequently associated with metastatic pheochromocytomas or SDHB mutations. However, a SDHB/D gene mutation has not been identified in the reported case. Although the patient needs careful monitoring following the surgery, to date she has been disease free for 12 months. This study could not find clear reasons for negative conversion, however, investigations of the negative conversion mechanism might reveal significant insights towards the improvement of patient survival.
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A case of dedifferentiated solitary fibrous tumor in the pelvis with TP53 mutation.
Virchows Arch.
PUBLISHED: 05-13-2014
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Solitary fibrous tumors (SFTs), initially observed in the pleura, were later found to develop in almost any extrapleural site. Dedifferentiation within SFTs was characterized only recently. We report a case of dedifferentiated SFT arising within the pelvis of a 70-year-old Japanese woman. Macroscopically, the resected tumor measured 17?×?17?×?13 cm. Histologically, the tumor displayed distinct heterologous osteosarcomatous and chondrosarcomatous components on a background of conventional SFT. Immunohistochemistry uncovered a loss of CD34 expression in the dedifferentiated area, whereas the nuclear expression of signal transducer and activator of transcription-6 (STAT6) and NGFI-A-binding protein 2 (NAB2) was maintained in both components. The p53 mutation 158 CGC > CAC (A158H) was found only in the dedifferentiated component. Furthermore, a fusion gene of NAB2(exon6)-STAT6(exon18) was detected in both the conventional and dedifferentiated components. The patient died of the disease 4 months after surgery. This case identifies a possible role of p53 dysfunction in the dedifferentiation process of SFT as reported in other sarcomas.
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Interpretation of HER2 tests in gastric cancer: confirmation of interobserver differences and validation of a QA/QC educational program.
Virchows Arch.
PUBLISHED: 02-23-2014
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Accurate testing for human epidermal growth factor 2 (HER2)-positive status is now mandatory to identify gastric cancer patients that will respond to trastuzumab treatment. Immunohistochemistry testing is the primary method used in hospitals. We performed a study of diagnostic accuracy by assessing interobserver variability in immunohistochemistry scoring of HER2 and determined the effectiveness of an educational program for general pathologists that used full sections of gastric cancer specimens. A first ring study (Japanese gastric cancer [JGC] ring study) was performed by five expert pathologists, using 50 whole surgical sections selected by a coordinator, to confirm interobserver discrepancies. A second study (quality assurance/quality control program) involved administration of an educational program to 49 general pathologists that consisted of (i) comments and explanation for a set of pre-educational program cases, (ii) a lecture, and (iii) presentation of typical and special cases for discussion. Effectiveness was measured by comparing indices of the difference between scores before and after the program. The JGC ring study demonstrated good agreement in the interpretation of HER2-immunohistochemistry. Kappa coefficients among the five observers were 0.73 (substantial) and 0.84 (almost perfect) in 4?×?4 and 3?×?3 cross tests, respectively. In the second study, the concordance rate and kappa coefficients improved from pre-educational program levels of 78.6 % and 0.68, respectively, to post-educational program levels of 87.1 % and 0.79, respectively. The present results suggest that effective educational programs reduce interobserver differences between pathologists and provide optimal information regarding patient selection for treatment.
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Distinct profile of HIF1?, PTCH, EphB2, or DNA repair protein expression and BRAF mutation in colorectal serrated adenoma.
J. Gastroenterol. Hepatol.
PUBLISHED: 01-23-2014
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The serrated colorectal carcinoma (CRC) as proposed to arise from serrated adenoma (SA) is characterized by upregulation of HIF1?, suppression of PTCH or EphB2, loss of DNA repair proteins, and BRAF mutation. The aim of this study was to evaluate alterations of these candidates involved in the serrated pathway in colorectal polyps.
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Distinct WNT/?-catenin signaling activation in the serrated neoplasia pathway and the adenoma-carcinoma sequence of the colorectum.
Mod. Pathol.
PUBLISHED: 01-14-2014
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Sessile serrated adenoma/polyp (SSA/P) is considered as an early precursor in the serrated neoplasia pathway leading to colorectal cancer development. The conventional adenoma-carcinoma sequence is associated with activation of the WNT signaling pathway, although its role in serrated lesions is still controversial. To clarify differences in WNT signaling activation in association with MLH1 methylation or BRAF/KRAS mutations between serrated and conventional routes, we performed ?-catenin immunostaining, methylation-specific PCR for MLH1 and WNT signaling associated genes such as AXIN2, APC, and MCC and secreted frizzled-related proteins (SFRPs), and direct sequencing of BRAF/KRAS in 27 SSA/Ps, 14 SSA/Ps with high-grade dysplasia and 9 SSA/Ps with submucosal carcinoma, as well as 19 conventional adenomas, 26 adenomas with high-grade dysplasia and 25 adenomas with submucosal carcinoma. Nuclear ?-catenin labelings were significantly lower in the serrated series than in their adenoma counterparts, and a significant increment in those labelings was found from SSA/Ps to those with high-grade dysplasia or submucosal carcinoma. The frequency of MLH1 and SFRP4 methylation was significantly higher in SSA/P series, as compared with corresponding adenoma series. AXIN2 and MCC were more frequently methylated in SSA/Ps with high-grade dysplasia and those with submucosal carcinoma than in adenoma counterparts. Stepwise increment of AXIN2 and MCC methylation was identified from SSA/Ps through those with high-grade dysplasia to those with submucosal carcinoma. A significant correlation was seen between nuclear ?-catenin expression and methylation of AXIN2 or MCC in the SSA/P series. BRAF mutation was more frequent, whereas KRAS mutation was less frequent in the SSA/P series as compared with the adenoma series. There was an inverse association of BRAF mutation with AXIN2 methylation in SSA/P series. In conclusion, WNT/?-catenin signal activation mediated by the methylation of SFRP4, MCC, and AXIN2 may make different contributions to colorectal neoplasia between the serrated and conventional routes.Modern Pathology advance online publication, 13 June 2014; doi:10.1038/modpathol.2014.41.
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Downregulation of sFRP-2 by epigenetic silencing activates the ?-catenin/Wnt signaling pathway in esophageal basaloid squamous cell carcinoma.
Virchows Arch.
PUBLISHED: 01-07-2014
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Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare variant of typical squamous cell carcinoma (SCC) associated with poor survival. A characteristic feature is nuclear accumulation of ?-catenin, without a mutation of the gene. We studied the methylation status of Wnt antagonist genes, such as secreted frizzled-related protein (sFRP) gene family members, Wnt inhibitory factor-1 (WIF-1), Dickkopf-1 (Dkk-1), and human Dapper protein-1 (HDPR-1), and alterations of the APC, Axin1, and Axin2 genes in 30 cases of esophageal BSCC. ?-catenin and sFRP (sFRP-1, sFRP-2, sFRP-4, sFRP-5) protein expression was examined by immunohistochemistry. APC, Axin1, and Axin2 gene mutations were detected in 3, 2, and 2 cases, respectively, and 6 cases (20 %) harbored at least 1 alteration in these genes. Methylation of the sFRP-2 promoter region was observed in all cases, and methylation was frequent in sFRP-1 and sFRP-5, but infrequent in Dkk-1, WIF-1, sFRP-4, and HDPR-1. sFRP-2 expression was almost completely absent in 25 cases (83 %), consistent with the methylation status. Nuclear accumulation of ?-catenin was observed in all cases. sFRP-5 expression was associated with a low nuclear ?-catenin labeling index. These results show that sFRP-2 is a target gene of hypermethylation in esophageal BSCC and suggest that sFRP-2 might contribute to BSCC tumorigenesis through the Wnt/?-catenin signaling pathway.
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A case of primary spindle cell variant of embryonal rhabdomyosarcoma of the prostate.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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We treated a rare case of spindle cell variant of embryonal rhabdomyosarcoma (RMS) of the prostate of a patient referred to our hospital for gross hematuria. Computed tomography and magnetic resonance imaging revealed a 4-cm-diameter mass with focal cystic change. Transurethral resection (TUR) of the prostate was performed to diagnosis and treat for complete urinary retention. Microscopically, the TUR specimen almost comprised a fascicular proliferation of spindle-shaped tumor cells, leading to the diagnosis of spindle cell sarcoma. The consequent total prostatectomy revealed the presence of rhabdomyoblasts in addition to the spindle cell proliferation. A MyoD1 p.L122R mutation was not detected in this tumor. The tumor recurred locally, with multiple metastatic lesions found soon after surgery. The patient received chemotherapy and radiation therapy but died 10 months after initial presentation. Although MyoD1 mutation is reported to define a clinically aggressive subset of embryonal RMS, spindle cell variant of embryonal RMS shows extremely adverse clinical outcomes irrespective of MyoD1 mutation.
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A case of Krukenberg carcinoma metastasized from colon cancer resembling mucinous cystadenocarcinoma of the ovary.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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We report a case of a 44-year-old woman with bilateral ovarian carcinoma that had metastasized from the colon and mimicked primary mucinous cystadenocarcinoma. Macroscopically, both ovarian tumors were large, multiloculated cystic masses with abundant mucinous content. Histologically, they were lined with mucinous epithelium with mild to moderate nuclear atypia and showed stromal invasion and surface involvement. At first, the tumors were diagnosed as bilateral primary ovarian mucinous cystadenocarcinomas. However, three months after surgery, a large villous tumor was discovered in the ascending colon by colonoscopic examination and was surgically resected. Histologically, the colonic tumor was a villous adenomatous tumor with invasive components of mucinous adenocarcinoma composed of well-differentiated adenocarcinoma and exhibited abundant extracellular mucin production. As a villous adenomatous component was present in the mucosal area, the colonic tumor was considered a primary tumor. Therefore, the original diagnosis of bilateral ovarian tumors was revised for consistent with metastasis from the colon carcinoma, in line with the findings of immunohistochemistry and loss of heterozygosity analysis. This case highlights the importance of considering the possibility of metastatic tumors from the gastrointestinal tract in the diagnosis of mucinous ovarian tumors.
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A case of dedifferentiated solitary fibrous tumor of the thoracic cavity.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Solitary fibrous tumors (SFTs), initially observed in the pleura, were later found to develop in almost any extrapleural site. Dedifferentiation within SFTs, a rare phenomenon, was characterized only recently, although it was previously described in soft tissue and bone tumors. We report a case of dedifferentiated SFT arising in the right pleura of a 69-year-old man. Computed tomography revealed a huge mass in the thoracic cavity. The tumor contained an area with a high degree of calcification and was heterogeneously enhanced. Macroscopically, the resected tumor was 175×145×135 mm in size. Morphologically and immunohistochemically, this was comprised of a typical SFT juxtaposed to a high-grade component including an osteosarcomatous component. These were sharply demarcated by thin fibrous septa. Furthermore, NAB2-STAT6 fusion transcripts were detected by reverse-transcriptase polymerase chain reaction in both conventional and high-grade components, supporting the concept of a dedifferentiation process in this tumor.
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Gastric adenocarcinoma of the fundic gland type (chief cell predominant type).
Endoscopy
PUBLISHED: 12-11-2013
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Gastric adenocarcinoma of the fundic gland (chief cell predominant type, GA-FG-CCP) was recently proposed as a new, rare variant of gastric adenocarcinoma. The aim of the current study was to evaluate the endoscopic features of GA-FG-CCP. A total of 10 GA-FG-CCPs were included and evaluated retrospectively. The endoscopic and clinicopathological features of the lesions were analyzed to provide information of diagnostic value. The GA-FG-CCPs were classified into two categories: submucosal tumor shape (60?%) and flat or depressed type (40?%). Endoscopically, the most common features were submucosal tumor shape (60?%), whitish color (70?%), dilated vessels with branching architecture (50?%), and background mucosa without atrophic change (90?%). GA-FG-CCP has distinct endoscopic characteristics, especially in terms of shape, color, vessels, and background mucosa and may be classified into two categories macroscopically. To diagnose GA-FG-CCP correctly by pathological examination of biopsy specimens, these endoscopic features should be taken into consideration.
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Histological subtypes and characteristic structures of HPV-associated oropharyngeal carcinoma; study with Japanese cases.
Diagn Pathol
PUBLISHED: 11-12-2013
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Human papillomavirus-associated oropharyngeal carcinoma (HPV-OPC) is clinicopathologically distinct entity from the HPV-unassociated one (nHPV-OPC). This study aimed to determine the relationship between histological subtypes of OPC and HPV status for Japanese cases and to identify histological structures of HPV-OPC.
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A case of neuroendocrine tumor G1 with unique histopathological growth progress.
World J Gastrointest Endosc
PUBLISHED: 10-24-2013
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A gastric neuroendocrine tumor (NET) is generated from deep within the tissue mucosal layers. In many cases, NETs are discovered as submucosal tumor (SMT)-like structures by forming a tumor mass. This case has a clear mucosal demarcation line and developed like a polyp. A dilated blood vessel was found on the surface. The mass lacked the yellow color characteristic of NETs, and a SMT-like form was evident. Therefore, a nonspecific epithelial lesion was suspected and we performed endoscopy with magnifying narrow-band imaging (M-NBI). However, this approach did not lead to the diagnosis, as we diagnosed the lesion as a NET by biopsy examination. The lesion was excised by endoscopic submucosal dissection. The histopathological examination proved that the lesion was a polypoid lesion although it was also a NET because the tumor cells extended upward through the normal gland ducts scatteredly. To our knowledge, there is no previous report of NET G1 with such unique histopathological growth progress and macroscopic appearance shown by detailed examination using endoscopy with M-NBI.
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Overexpression of regenerating gene I? appears to reflect aberration of crypt cell compartmentalization in sessile serrated adenoma/polyps of the colon.
Diagn Pathol
PUBLISHED: 10-07-2013
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Colorectal sessile serrated adenoma/polyps (SSA/Ps) are characterized by asymmetrical distribution of Ki67-positive cells, which varies among crypts and involves the crypt length to a variable extent; the pattern has been designated as aberration of crypt cell compartmentalization. The regenerating gene (REG) I? is a cell growth and/or anti-apoptotic factor and its overexpression might be associated with aberration of crypt cell compartmentalization in SSA/Ps. We investigated REG I? expression in SSA/Ps in comparison to hyperplastic polyps (HPs).
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Digestive disease management in Japan: a report on the 6th diagnostic pathology summer fest in 2012.
Digestion
PUBLISHED: 09-18-2013
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The 6th Diagnostic Pathology Summer Fest, held in Tokyo on August 25-26, 2012, opened its gates for everyone in the medical profession. Basic pathology training can contribute to the improvement of algorithms for diagnosis and treatment. The 6th Summer Fest with the theme Pathology and Clinical Treatment of Gastrointestinal Diseases was held at the Ito International Research Center, The University of Tokyo. On August 25, Treatment of Early Gastrointestinal Cancer and New Guidelines was discussed in the first session, followed by Biopsy Diagnosis of Digestive Tract: Key Points of Pathological Diagnosis for Inflammation and Their Clinical Significance in the second session. On August 26, cases were discussed in the third session, and issues on pathological diagnosis and classification of neuroendorcrine tumor in the fourth session. The summaries of speeches and discussions are introduced along with the statements of each speaker. This meeting was not a formal evidence-based consensus conference, and 20 experts gave talks on their areas of specialty. Discussion was focused on how the management strategy should be standardized on the algorithm of patient care. © 2013 S. Karger AG, Basel.
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Long-term follow-up of gastric adenocarcinoma with chief cell differentiation using upper gastrointestinal tract endoscopy.
Intern. Med.
PUBLISHED: 07-15-2013
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During upper endoscopic screening, a 71-year-old asymptomatic woman was found to have a small, yellowish, superficial elevated lesion in the upper third of her stomach, without any signs of atrophic mucosa. The patient underwent endoscopic follow-up once a year for approximately five years; however, changes in the tumor were barely detectable. Endoscopic mucosal resection was performed, and a histological examination confirmed the diagnosis of gastric adenocarcinoma with chief cell differentiation (GA-CCD). GA-CCD is rare; therefore, its clinicopathological features remain unknown. This case suggests that only barely detectable endoscopic changes may be observed in GA-CCD during long-term follow-up.
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Protein expression and methylation of DNA repair genes hMLH1, hMSH2, MGMT and BRCA1 and their correlation with clinicopathological parameters and prognosis in basal-like breast cancer.
Histopathology
PUBLISHED: 06-30-2013
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Basal-like breast cancer (BLBC) is characterized by aggressive behaviour; its genesis is the perturbation of DNA repair as a consequence of BRCA1 methylation or mutation. We comparatively evaluated alterations of DNA repair proteins and p53 between BLBC and non-BLBC cases.
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Histological assessment of intra- and inter-institutional reliabilities in detection of desmoplastic reaction in biopsy specimens of early colorectal carcinomas.
Pathol. Int.
PUBLISHED: 05-29-2013
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We previously reported a relationship between depth of submucosal invasion of early colorectal carcinomas and desmoplastic reaction (DR). However, poor inter-observer agreement on the histopathological diagnosis of DR in biopsy specimens with hematoxylin and eosin (H&E) staining has been the major critique of this tool. In this study, reproducibility of the histopathological diagnosis of DR was evaluated. Furthermore, we investigated the possible improvement of the reproducibility after education about histological characteristics and tried to identify histological characteristics that are most important in the recognition of DR. A total of 34 H&E stained slides were included in this study and analyzed by three pathologists. Slides were reviewed before and after education about histological characteristics of DR. Kappa statistics were used to compare the inter-observer variability. We investigated the relationship between DR and histopathological factor. The inter-observer agreement during the first session varied between 0.30 and 0.63, which improved during the second session toward an agreement between 0.58 and 0.71. Myofibroblast proliferation associated with cancer invasion was found to be the most useful in the diagnosis of DR. In conclusion, the correct detection of myofibroblasts may facilitate the standardization of diagnosis of DR.
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p53 mutations may be involved in malignant transformation of giant cell tumor of bone through interaction with GPX1.
Virchows Arch.
PUBLISHED: 05-28-2013
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Giant cell tumor of bone (GCTB) is a benign tumor with a tendency for local recurrence. Secondary malignant GCTB is rare, occurring in less than 2 % of GCTB cases. Mechanisms of malignant transformation of GCTB remain unclear. We examined 43 cases of GCTB (38 conventional cases, two lung implantation cases, and three secondary malignant cases) for p53 gene mutations and for loss of heterozygosity (LOH) of p53 when corresponding normal tissue was available. In addition, to elucidate the possible involvement of p53, GPX-1, cyclinD1, and Ki-67 in malignant transformation of GCTB, we assessed the expression of these proteins by immunohistochemistry. Mutations or LOH of p53 were found in all three malignant cases, which also showed p53 overexpression. Non-synonymous p53 mutations were detected in seven of 38 conventional cases (18 %), although none of these showed p53 overexpression, defined as more than 10 % of cells being positive. LOH at the p53 locus was detected in eight of 37 informative cases, although this was not associated with p53 overexpression in conventional GCT. Expression of GPX-1 was higher in the recurrent group, which included metastatic and malignant cases, and patients with high GPX-1 expression were at greater risk for early relapse. We also observed a positive correlation between high p53 expression and high GPX-1 expression in GCTB. Given that GPX-1 is shown to be a target of p53, these results suggest that p53 mutations play a role in tumor recurrence and malignant transformation of GCTB through interactions with GPX-1.
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The prognostic value of pfetin: a validation study in gastrointestinal stromal tumors using a commercially available antibody.
Jpn. J. Clin. Oncol.
PUBLISHED: 04-25-2013
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Adjuvant treatment with imatinib mesylate is an effective treatment for gastrointestinal stromal tumor. However, 50% of patients with gastrointestinal stromal tumor can be cured by surgery alone; hence, risk stratification for therapy with imatinib mesylate is the next challenge. Previously, using a proteomic approach, we discovered a potential prognostic biomarker for gastrointestinal stromal tumor, pfetin, and immunohistochemically validated its clinical utility using our original monoclonal antibody. In the present study, we examine the usefulness of a commercially available polyclonal antibody against pfetin.
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Right ventricular electrical remodeling and arrhythmogenic substrate in rat pulmonary hypertension.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 04-23-2013
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Right ventricular (RV) dysfunction, caused by severe pulmonary hypertension (PH), is associated with high mortality because of RV failure. However, some patients can suffer from sudden cardiac death (SCD). We hypothesized that severe PH can cause RV arrhythmogenesis, leading to SCD. We sought to investigate arrhythmogenesis in PH. Optical mapping analysis (OMP) with an electrophysiological study (EPS) and pathological examination were performed in a monocrotaline (MCT)-induced rat PH model. Rats were injected with MCT (60 mg/kg), and OMP was performed in isolated Langendorff-perfused hearts. OMP revealed abnormal RV conduction delays and abnormal patterns, along with elevated RV pressure. In addition, impaired action potential duration dispersion (APDd), an index of myocardial repolarization instability, was observed only in the RVs with severe PH. The EPS demonstrated that lethal arrhythmias were induced by burst pacing to the RV when deteriorated APDd became evident. This arrhythmogenesis was inhibited by combination treatment with sildenafil and beraprost (SIL + BERA). RT-PCR showed an mRNA up-regulation of Type I collagen and down-regulation of connexin-43 in the RV at 5 weeks after MCT injection. Pathological examination revealed pulmonary vascular remodeling and RV hypertrophy with interstitial fibrosis, which was substantially reduced by SIL + BERA. Immunohistochemistry also revealed connexin-43 degradation in the RVs with severe PH. In contrast, connexin-43 was well preserved, and no lethal arrhythmias were induced by burst pacing to the RV in the absence of PH after SIL + BERA. In conclusion, RV electrical remodeling, including impaired APDd, causes arrhythmogenesis in severe PH, potentially associated with SCD attributable to PH.
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A white opaque substance-positive gastric hyperplastic polyp with dysplasia.
World J. Gastroenterol.
PUBLISHED: 03-24-2013
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The endoscopic findings of gastric hyperplastic polyps (HPs) with dysplasia have not been well-defined, and the clinical significance of these lesions, including their malignant potential, is unclear. In this report, we describe a case of a white opaque substance (WOS)-positive gastric HP with dysplasia. A 76-year-old woman was referred to our hospital for endoscopic resection of a gastric HP. Upper endoscopy revealed a 25-mm whitish and reddish polypoid lesion on the greater curvature in the lower third of the stomach. The whitish part was diagnosed as a WOS using conventional and magnifying endoscopy with narrow band imaging. An examination of the biopsy specimen indicated that the lesion was a typical gastric HP. However, because of its color and the presence of a WOS, we suspected that this lesion was an atypical gastric HP. Therefore, we performed a polypectomy. Histopathologically, diffuse low- to high-grade dysplasia was found on the surface of the polyp. We performed immunohistochemical staining using a monoclonal antibody specific for adipophilin as a marker of lipid droplets (LDs). LDs were detected in approximately all of the neoplastic cells, especially in the surface epithelium of the intervening apical parts and were located in the subnuclear cytoplasm of the neoplastic cells. According to endoscopic and histopathological findings, the WOS-positive epithelium indicated dysplasia of the gastrointestinal phenotype, which could absorb lipids. The presence of a WOS in a gastric HP may be considered an endoscopic finding that is predictive of the neoplastic transformation of a gastric HP. We suggest that a WOS-positive gastric HP should be resected endoscopically to investigate its neoplastic transformation.
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Alteration in the Wnt/?-catenin signaling pathway in gastric neoplasias of fundic gland (chief cell predominant) type.
Hum. Pathol.
PUBLISHED: 02-19-2013
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Gastric neoplasia of chief cell-predominant type (GN-CCP) has been reported as a new, rare variant of gastric tumor. GN-CCPs were defined as tumors consisting of irregular anastomosing glands of columnar cells mimicking chief cells of fundic gland with nuclear atypia and prolapse-type submucosal involvement. We comparatively evaluated clinicopathologic features between 31 GN-CCPs and 130 cases of conventional gastric adenocarcinoma invading into submucosa (CGA-SM) in addition to nuclear ?-catenin immunolabeling and direct sequencing of members of the Wnt/?-catenin pathway, CTNNB1, APC, and AXIN, in a subset of these tumors. GN-CCP presented as small protruded lesions located in the upper third of the stomach, with minimal involvement into the submucosa and rare lymphovascular invasion. None of the lesions have demonstrated a recurrence of disease or metastasis on follow-up. Nuclear ?-catenin immunolabeling was higher in GN-CCP (labeling index [LI]: median, 19.3%; high expresser [LI >30%], 7/27 cases [26%]) than CGA-SM (median LI, 14.7%; high expresser, 1/19 cases [6%]). Missense mutation of APC was observed in 1 GN-CCP but not CGA-SM. Missense or nonsense mutations of CTNNB1 and AXIN1 were higher in GN-CCPs (14.8%, both) than CGA-SMs (5.3%, both). Missense mutations of AXIN2 were higher in GN-CCPs (25.9%) than in CGA-SMs (10.5%). Overall, 14 (51.9%) of 27 GN-CCPs and 5 (26.3%) of 19 CGA-SM cases harbored at least 1 of these gene mutations. In conclusion, GN-CCPs as a unique variant of nonaggressive tumor are characterized by nuclear ?-catenin accumulation and mutation of CTNNB1 or AXIN gene, suggesting activation of the Wnt/?-catenin pathway.
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Development and clinical usability of a new traction device "medical ring" for endoscopic submucosal dissection of early gastric cancer.
Surg Endosc
PUBLISHED: 02-15-2013
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Although various traction devices exist for endoscopic submucosal dissection (ESD), the effects of the material used in the devices on the human body has not been considered. Moreover, there has been no report on a device that facilitates dissection both on the oral and anal side of the lesion. We made a traction device that has no deleterious effects on the body and is noninvasive, easy to use, and enables a bilateral approach in ESD. We report the process of its creation and a prospective evaluation of its usage in actual ESD procedures.
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Galectin-4, a novel predictor for lymph node metastasis in lung adenocarcinoma.
PLoS ONE
PUBLISHED: 01-01-2013
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Metastasis is still a major issue in cancer, and the discovery of biomarkers predicting metastatic capacity is essential for the development of better therapeutic strategies for treating lung adenocarcinoma. By using a proteomic approach, we aimed to identify novel predictors for lymph node metastasis in lung adenocarcinoma. Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis showed 6 spots differentially expressed between lymph node metastasis-positive and lymph node metastasis-negative groups in a discovery set. Subsequent mass spectrometry showed that 2 of these spots were derived from galectin-4, and western blot analysis confirmed the overexpression of galectin-4 in metastatic samples. The predictive value of galectin-4 was confirmed by immunohistochemical analysis for a validation set consisting of 707 surgically resected specimens of lung adenocarcinomas (stages I to IV). We observed that 148 lung adenocarcinomas (20.9%) expressed galectin-4, which was significantly associated with variables of disease progression such as tumor size (p<0.0001), pleural invasion (p?=?0.0071), venous invasion (p?=?0.0178), nodal status (p?=?0.0007), and TNM stage (p<0.0001). By the multivariate analysis, Galectin-4 expression was revealed as one of the independent predictor for lymph node metastasis, together with solid predominant and micropapillary histologic pattern. Furthermore, galectin-4 expression was revealed to be an independent predictor for lymph node metastasis and an adverse survival factor in patients with lung adenocarcinoma of acinar predominant type. Galectin-4 plays an important role in metastatic process of lung adenocarcinoma. Immunohistochemical testing for galectin-4 expression may be useful together with the detection of specific histology to predict the metastatic potential of lung adenocarcinoma.
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A case of bilateral renal cell carcinoma associated with long-term dialysis showing false-positive immunoreactivity for TFE3 as Xp11 translocation renal cell carcinoma.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2013
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Renal carcinomas associated with Xp11.2 translocations/transcription factor 3 (TFE3) gene fusion (Xp11 translocation RCC) are a rare subtype of renal cell carcinoma. A middle-aged Japanese man, who had a medical history of dialysis for more than 12 years, had bilateral renal cancers with a background of acquired cystic disease of the kidney and remarkable deposition of calcium oxalate in the tumorous area. The right renal tumor showed papillary architecture of clear cells with diffuse and strong immunoreactivity for TFE3 and focal and weak positivity for cathepsin K, suggesting a possibility of Xp11 translocation RCC. However, RT-PCR failed to detect any type of the reported fusion genes involving TFE3. Thus, the sample was sent for a TFE3 break-apart FISH assay in a renal tumor consultation service, which reported no evidence of TFE3 gene rearrangement. The right renal tumor was finally diagnosed as papillary renal cell carcinoma with cystic change. We report here a case of bilateral renal cell carcinoma in a patient undergoing long-term dialysis, which showed false-positive immunoreactivity for TFE3 immunostaining. Titration of TFE3 immunohistochemical staining (IHC) should be performed and cross-referenced with the FISH or RT-PCR results to avoid the misinterpretation of TFE3 IHC results.
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Desmoplastic fibroma of the scapula with fluorodeoxyglucose uptake on positron emission tomography: a case report and literature review.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2013
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We present a case of desmoplastic fibroma (DF) arising from the right scapula that was incidentally identified by fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging performed to evaluate the presence of metastasis due to a history of surgical treatment for endometrioid adenocarcinoma. A 65-year-old woman was admitted to our hospital for consultation about a bone lesion in the right scapula although she was asymptomatic. FDG-PET revealed moderate focal (18)F-FDG uptake in the right scapula with a maximal standardized uptake value of 3.2. The lower angle of the scapula was unclear on plain radiology. Needle biopsy was performed to make a differential diagnosis between primary bone and metastatic tumor. Pathologically, the tumor was composed of a relatively sparse proliferation of spindle-shaped fibroblastic/myofibroblastic cells in a dense collagenous background. Therefore, the diagnosis was a primary fibrous bone tumor. Wide excision was performed, because of the possibility of malignant tumors such as low-grade fibrosarcoma in light of the FDG-PET uptake. Pathologically, the resected tumor was composed of a proliferation of less atypical spindle cells in the collagenous stroma with focally myxoid change; no mitotic figures were observed. Immunohistochemically, ?-catenin nuclear/cytoplasmic staining was not observed, and no ?-catenin genetic mutations were detected. Therefore, the tumor was diagnosed as DF. DF is a tumor that exhibits FDG-PET uptake. There were no signs of recurrence 6 months after surgery.
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Gene expression network analysis of ETV1 reveals KCTD10 as a novel prognostic biomarker in gastrointestinal stromal tumor.
PLoS ONE
PUBLISHED: 01-01-2013
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Prognostic biomarkers are required for risk stratification therapy in the patients with gastrointestinal stromal tumor (GIST). In this study, we aimed to identify prognostic biomarkers in GIST. We assessed the prognostic value of E twenty-six variant 1 (ETV1), a recently identified transcription factor unique to GIST. We also examined the clinical utility and functions of its downstream gene, potassium channel tetramerization domain containing protein 10 (KCTD10).
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A case of myxoid liposarcoma of the breast.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2013
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A 70-year-old woman visited a local hospital complaining of a nodulein the right breast, present since 1 month. She was referred to our hospital for further evaluation. Following mammotome (MMT) biopsy, the nodule was diagnosed as myxoid/round cell liposarcoma. She underwent total mastectomy of the right breast. Histological analysis indicated that the tumor was almost entirely composed of proliferating small round mesenchymal cells in amyxoid matrix background with capillary-like vessels with partial necrosis (<10%). Immunohistochemically, p53 positive cells were seen focally (<1%) only, and the Ki-67 labeling index was approximately 20%. Sincethe surgical margin was histologically positive despite pathologic findings of high-grade malignancy, adjuvant treatment involving local radiation therapy (60Gy) was administered. The patient was free from any symptoms of local recurrence and metastases 1 year and 8 months after surgery.
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Clear cell variant of squamous cell carcinoma originating in the esophagus: report of a case with immunohistochemical and oncogenetic analyses.
Pathol. Int.
PUBLISHED: 11-30-2011
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The cutaneous clear cell squamous cell carcinoma (SCC) is a rare tumor thought to be associated with hair follicle or skin appendage differentiation. We report herein a rare variant case of a clear cell SCC originating in the esophagus. A 70-year-old Japanese man was found to have a tumor in the esophagus. The excised neoplasm showed dominance of clear cell over conventional SCC components; the two components in an apparent continuum. The clear cells, regular in size with a moderate nuclear/cytoplasmic ratio and relatively hyperchromatic and centrally located nuclei, were compactly arranged in sheets. Glycogen deposition was apparent on PAS staining with or without diastase digestion and under the electron microscope. The clear cell SCC components were positive for cytokeratin (CK)7, CK8, CK18 and CK19, but were negative for CK5/6 or CK14. Reciprocal staining patterns of CKs were apparent in conventional SCC components. The present case and cutaneous clear cell SCC counterparts share some histopathologic characteristics whereas CKs expression differs between the two. Overexpression of p53 protein, without evidence of any mutation, and reduced p16(INK4a) were noted in both clear cell and conventional SCC components. No mutations of Kras, BRAF or ?-catenin genes were found in both tumor components.
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Nuclear atypia grading score is a useful prognostic factor in papillary gastric adenocarcinoma.
Histopathology
PUBLISHED: 11-19-2011
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To investigate nuclear atypical in papillary gastric adenocarcinoma (PGA).
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Expression of activation-induced cytidine deaminase in ulcerative colitis-associated carcinogenesis.
Histopathology
PUBLISHED: 11-01-2011
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Activation-induced cytidine deaminase (AID) is a DNA/RNA-editing enzyme that is essential for hypermutation and class-switch recombination in immunoglobulin genes. The aim of this study was to investigate the expression of AID and its association with p53 mutation in ulcerative colitis (UC)-associated carcinogenesis.
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miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma.
Blood
PUBLISHED: 10-31-2011
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Many transformed lymphoma cells show immune-phenotypes resembling the corresponding normal lymphocytes; thus, they provide a guide for proper diagnosis and present promising routes to improve their pathophysiologic understanding and to identify novel therapeutic targets. However, the underlying molecular mechanism(s) of these aberrant immune-phenotypes is largely unknown. Here, we report that microRNA-135b (miR-135b) mediates nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-driven oncogenicity and empowers IL-17-producing immunophenotype in anaplastic large cell lymphoma (ALCL). NPM-ALK oncogene strongly promoted the expression of miR-135b and its host gene LEMD1 through activation of signal transducer and activator of transcription (STAT) 3. In turn, elevated miR-135b targeted FOXO1 in ALCL cells. miR-135b introduction also decreased chemosensitivity in Jurkat cells, suggesting its contribution to oncogenic activities of NPM-ALK. Interestingly, miR-135b suppressed T-helper (Th) 2 master regulators STAT6 and GATA3, and miR-135b blockade attenuated IL-17 production and paracrine inflammatory response by ALCL cells, indicating that miR-135b-mediated Th2 suppression may lead to the skewing to ALCL immunophenotype overlapping with Th17 cells. Furthermore, antisense-based miR-135b inhibition reduced tumor angiogenesis and growth in vivo, demonstrating significance of this "Th17 mimic" pathway as a therapeutic target. These results collectively illuminated unique contribution of oncogenic kinase-linked microRNA to tumorigenesis through modulation of tumor immune-phenotype and microenvironment.
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Prevalence of uterine and adnexal involvement in pulmonary lymphangioleiomyomatosis: a clinicopathologic study of 10 patients.
Am. J. Surg. Pathol.
PUBLISHED: 10-25-2011
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Lymphangioleiomyomatosis (LAM), a systemic disorder affecting almost exclusively young women, is characterized by the abnormal proliferation of smooth muscle-like cells (LAM cells). LAM can occur either in association with the tuberous sclerosis complex (TSC) (TSC-LAM) or without TSC (sporadic LAM). Recent studies have demonstrated that LAM is a neoplasm arising from constitutive activation of the mammalian target of rapamycin signaling pathway dysregulated by a functional loss of TSC genes, but the primary organ of origin remains unclear. Therefore, we performed histologic and immunohistologic analyses of gynecologic organs in 20 patients, half with and the other half without pulmonary LAM, to determine how often LAM involves the uterus. The results showed that 9 of 10 (90%) patients with pulmonary LAM had uterine LAM lesions. In contrast, no patients without pulmonary LAM had so. All uterine LAM lesions were accompanied by LAM lesions in retroperitoneal or pelvic lymph nodes and LAM cell clusters, each enveloped by a monolayer of vascular endothelial growth factor receptor-3-positive lymphatic endothelial cells. Furthermore, when we compared uterine lesions of TSC-LAM with those of sporadic LAM, proliferation of HMB45-positive epithelioid-shaped LAM cells and infiltrates with a tongue-like growth pattern was more prominent in the former, whereas the extent of lymphangiogenesis within the myometrium was greater in the latter. These results indicate that uterine involvement is a common manifestation of LAM, and, possibly, that the uterus or an adjacent locale in the retroperitoneum or pelvic cavity is the primary site of origin of LAM.
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Clinical proteomics identified ATP-dependent RNA helicase DDX39 as a novel biomarker to predict poor prognosis of patients with gastrointestinal stromal tumor.
J Proteomics
PUBLISHED: 08-30-2011
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Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract, comprising a wide spectrum from a curable disorder to highly malignant disease. GIST is characterized by tyrosine kinase mutations, and molecular targeting therapies against these abnormal enzymes require prognostic biomarkers. To identify candidate prognostic biomarkers, we examined proteomic features corresponding to metastasis after surgery. Using two-dimensional difference gel electrophoresis with a large format gel, we compared the primary tumor tissues of GIST patients free of metastasis for two years after surgery (eight cases) with those of patients who developed metastasis within one year after surgery (nine cases). We found the intensities of 38 protein spots to differ significantly between the two groups. Mass spectrometric protein identification revealed that these corresponded to 25 unique genes. Immunohistochemical validation demonstrated ATP-dependent RNA helicase DDX39 to be significantly associated with metastasis and poor clinical outcomes in a group of 72 GIST patients. In conclusion, we have established a novel prognostic utility of ATP-dependent RNA helicase DDX39 in GIST.ATP-dependent RNA helicase DDX39, a novel biomarker for GIST likely to be associated with metastatic disease, can identify patients likely to benefit from new therapeutic strategies such as tyrosine kinase inhibitors.
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Gastric adenocarcinoma of fundic gland type (chief cell predominant type) treated with endoscopic aspiration mucosectomy.
Dig Endosc
PUBLISHED: 06-25-2011
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Upper endoscopy screening in an asymptomatic 56-year-old man showed a small, yellowish elevated lesion with a central depression on the posterior wall in the gastric cardia. Biopsy specimens from this lesion were suspicious of carcinoid tumor. We suspected this lesion to be a sporadic gastric carcinoid tumor with a diameter of 5 mm, limited to the mucosal layer. We then performed an endoscopic aspiration mucosectomy with a cap-fitted endoscope. Microscopically, the lesion obtained from the resected specimen was minimally invasive to the submucosa and showed highly differentiated columnar cells in irregularly anastomosing glands. Immunohistology was positive for pepsinogen-I, and MUC6, partially positive for H(+)/K(+)-ATPase, and negative for MUC5AC. In addition, it was positive for synaptophysin and CD56, and negative for chromogranin A. We finally diagnosed the patient as having gastric adenocarcinoma of fundic gland type (chief cell predominant type) with minimal invasion (100 µm) to the submucosa. Surveillance endoscopy with biopsy specimens and abdominal computed tomography at 1 year revealed no evidence of tumor recurrence. We herein report this rare case of gastric adenocarcinoma of fundic gland type (chief cell predominant type).
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Ectopic pancreas presenting as a submucosal gastric tumor: case report and literature review.
Pediatr. Surg. Int.
PUBLISHED: 05-27-2011
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Ectopic pancreas is of little clinical significance. We report a case of ectopic pancreas in a 2-year-old girl presenting as a heterogeneous solid submucosal tumor of the posterior wall of antrum proximal to the pylorus, treated by distal gastrectomy and Billroth I reconstruction. We reviewed 15 cases in the English literature.
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Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients.
Cancer Chemother. Pharmacol.
PUBLISHED: 05-22-2011
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To evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in patients with locally advanced basal-like breast cancers (BLBCs).
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The usefulness of NBI magnification on diagnosis of superficial esophageal squamous cell carcinoma.
Dig Endosc
PUBLISHED: 05-04-2011
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Reported herein is the case of a 80-year-old man who had small squamous cell carcinoma in the esophagus. The lesion was initially detected as a irregular reddish elevated and flat area depicted by non-magnified white light endoscopy and observed as a brownish area with the narrow-band imaging system (NBI). The depth of elevated and depressed area in the lesion was predicted to be LSM to MM due to Inoues classification of morphologic change of intrapapillary capillary loop (IPCL) under magnified NBI observation. The depth of another flat area was not able to predicted by Inoues classification, and we used Arimas classification. We predicted the depth of invasion to be MM to SM1.by this classification. Endoscopic submucosal dissection (ESD) was carried out for the lesion. As a result, the endoscopic diagnosis completely accorded with pathological diagnosis. We could diagnose correctly by adding Arimas classification to Inoues classification.
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Role of narrow band imaging for diagnosis of early-stage esophagogastric cancer: current consensus of experienced endoscopists in Asia-Pacific region.
Dig Endosc
PUBLISHED: 05-04-2011
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In Asian countries, squamous cell carcinoma is the most common type of esophageal cancer, and the incidence of gastric cancer remains have plateaued. To synthesize current information and to illustrate its clinical benefit of narrow band imaging (NBI) for diagnosis of superficial esophageal squamous carcinoma (SESCC) and early gastric cancer (EGC), a consensus conference was held by a panel of nine experts from Asian-Pacific countries. The experts agreement suggested importance of interpretation of both vascular architecture and surface structure of the lesions and proper processor settings for endoscopic images. Zoom endoscopy was not regarded as absolutely necessary for detection of SESCC, but magnifying observation provided valuable information for characterization of detected lesions in the esophagus and the stomach. In general, NBI is useful for detection and characterization of SESCC, whereas it is beneficial mainly for characterization of EGC. Chromoendoscopy was found to be still worthwhile in certain situations, such as determination of the extent of SESCC by Lugols staining, or detection and delineation of EGC by indigo carmine. NBI could replace chromoendoscopy in routine examination because it is easy to use and adds much information to conventional WLI, but it cannot eliminate chromoendoscopy when we make a final diagnosis for treatment decision-making. Consequently, the benefit of NBI or magnifying NBI is specific for the organ and the purpose of the examination, thus optimum indication and usage should be understood for maximum clinical benefit.
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A case of de novo secondary malignant giant-cell tumor of bone with loss of heterozygosity of p53 gene that transformed within a short-term follow-up.
Pathol. Res. Pract.
PUBLISHED: 04-20-2011
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A 19-year-old woman was admitted to the hospital with a complaint of right wrist pain. A plain radiograph showed an osteolytic lesion in the right distal radius. Surgical treatment with curettage and bone grafting was performed under the clinical diagnosis of a giant-cell tumor. However, local recurrence was noticed 6 months after the treatment, and the curettage and bone graft were performed again. The histology of the recurrent lesion revealed a malignant giant-cell tumor that was entirely composed of highly atypical stromal cells and tumor giant cells. After a retrospective review of the primary lesion, it was found to also contain a small focus of pleomorphic cells within the conventional giant-cell tumor. Immunohistochemical and genetic analysis revealed p53 overexpression in the tumor giant cells and loss of heterozygosity of p53 gene only in the recurrent tumor; thus, a diagnosis of secondary malignant giant-cell tumor was finally made. The patient underwent systemic chemotherapy along with curettage and cryosurgery using liquid nitrogen. It is now 1 year and 4 months after the last treatment, and the patient is well and alive with no evidence of the disease. Identification of p53 genetic alteration may help in diagnosing malignant giant-cell tumor.
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Chlamydophila pneumoniae attachment and infection in low proteoglycan expressing human lymphoid Jurkat cells.
Microb. Pathog.
PUBLISHED: 03-19-2011
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This study investigated the proteoglycan (PG)-dependent mechanism of Chlamydophila pneumoniae attachment to lymphocytic cells. Lymphoid Jurkat cells and epithelial HEp-2 cells were statically infected with C. pneumoniae (TW183). Transmission electron microscopy and assessment of inclusion-forming units indicated that the bacteria grew normally in Jurkat cells and were capable of producing secondary infection; however, they grew at a slower rate than in HEp-2 cells. RT-PCR analysis indicated that HEp-2 cells strongly expressed PG-core protein encoding genes, thereby sustaining glycosaminoglycans (GAGs), such as heparin, on the cellular surface. Similar gene expression levels were not observed in Jurkat cells, with the exception of glypican-1. Immunofluorescence analysis also supported strong heparin expression in HEp-2 cells and minimal expression in Jurkat cells, although heparan sulfate pretreatment significantly inhibited bacterial attachment to both cell types. Immunofluorescent co-staining with antibodies against chlamydial LPS and heparin did not identify bacterial and heparin co-localization on Jurkat cells. We also confirmed that when C. pneumoniae was statically infected to human CD4(+) peripheral blood lymphocytes known not expressing detectable level of heparin, the bacteria attached to and formed inclusion bodies in the cells. Thus, the attachment mechanism of C. pneumoniae to Jurkat cells with low PG expression is unique when compared with HEp-2 cells and potentially independent of GAGs such as heparin.
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Aberrant activation-induced cytidine deaminase expression is associated with mucosal intestinalization in the early stage of gastric cancer.
Virchows Arch.
PUBLISHED: 03-07-2011
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Although Helicobacter pylori is a risk factor for gastric cancer (GC), its detailed carcinogenesis remains unclear. Recently, aberrant expression of activation-induced cytidine deaminase (AID) was demonstrated in gastric epithelium with H. pylori infection and seems to cause the accumulation of mutation. This investigation aims to elucidate whether or not AID expression plays an important role in the carcinogenesis of early GC. We examined the correlation between immunohistochemical AID expression and histological characteristics, including pre-existing chronic gastritis and cellular mucin phenotype in 138 cases of intramucosal GC. Furthermore, we investigated the relationship between AID, p53 protein, and ?-catenin. The low degree of polymorphonuclear neutrophil activity, and the high degree of glandular atrophy and intestinal metaplasia were significantly correlated with the high levels of AID expression in non-neoplastic mucosa (P?=?0.007, P???0.001, and P?=?0.003). With regard to mucin phenotype of carcinoma, the intestinal phenotype tended to have the higher AID expression levels (P?=?0.052). AID showed close correlations with Cdx2 and nuclear staining of ?-catenin (P?=?0.003, P?=?0.034). As for p53 protein, no correlation was found with AID expression. Our findings suggest that aberrant AID expression is correlated with persistent inflammatory condition induced by H. pylori infection and may contribute to the development of GC through an inflammatory condition and intestinalization.
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Cluster analysis of claudin-1 and -4, E-cadherin, and ?-catenin expression in colorectal cancers.
J Surg Oncol
PUBLISHED: 02-24-2011
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Intercellular adhesion mediated by the claudin and cadherin/catenin complex is a prerequisite for epithelial integrity and differentiation, and has been suggested to be frequently disturbed in cancers. The aim of this study was to assess the relationship between such abnormality and clinicopathological features of colorectal carcinomas.
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Autofluorescence imaging endoscopy for identification and assessment of inflammatory ulcerative colitis.
World J. Gastroenterol.
PUBLISHED: 02-16-2011
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To validate the clinical relevance of autofluorescence imaging (AFI) endoscopy for the assessment of inflammatory ulcerative colitis (UC).
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Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy-associated T cell lymphoma in Japan.
Histopathology
PUBLISHED: 02-16-2011
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To elucidate the clinicopathological findings of primary intestinal enteropathy-associated T cell lymphoma (EATL) in Japan, a non-endemic area for coeliac disease.
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Oncocytic mucoepidermoid carcinoma of the parotid gland with CRTC1-MAML2 fusion transcript: report of a case with review of literature.
Hum. Pathol.
PUBLISHED: 02-14-2011
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Oncocytic mucoepidermoid carcinoma is a very rare variant of mucoepidermoid carcinoma, composed predominantly of oncocytic cells. Most previously reported cases described the difficulty in histologic differentiation from other oncocytic tumors. Here we report a case of oncocytic mucoepidermoid carcinoma of parotid gland diagnosed by the detection of CRTC1-MAML2 fusion. A 53-year-old man had a left superficial parotidectomy conducted for 3-cm-sized mass. The resected tumor was composed almost exclusively of oncocytic tumor cells. With detailed histologic evaluation, scarce vacuolated tumor cells, suggestive of mucous cell of mucoepidermoid carcinoma, and one focus of tumor embolism in a vein were found, suggesting the possibility of oncocytic mucoepidermoid carcinoma. Immunohistochemically, oncocytic cells were diffusely positive for p63. Reverse transcriptase polymerase chain reaction and direct sequencing revealed CRTC1-MAML2 translocation of this tumor. To our knowledge, this report describes the first case of oncocytic mucoepidermoid carcinoma confirmed with CRTC1-MAML2 fusion. Identification of this fusion gene may help in distinguishing oncocytic mucoepidermoid carcinoma from its mimics.
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Sessile serrated adenoma with early neoplastic progression: a clinicopathologic and molecular study.
Am. J. Surg. Pathol.
PUBLISHED: 01-26-2011
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Sessile serrated adenoma (SSA), also referred to as sessile serrated polyp, has been proposed as a precursor lesion to microsatellite unstable carcinoma. However, the mechanism of stepwise progression from SSA to early invasive carcinoma has been unclear. The purpose of this study was to elucidate the histologic characteristics and possible role of p53, ?-catenin, BRAF, KRAS, and PIK3CA in the development and progression of SSA. We analyzed 12 cases of SSA with neoplastic progression (SSAN), including 7 cases of intraepithelial high-grade dysplasia (HGD) and 5 cases of submucosal invasive carcinoma, and compared them with 53 SSAs and 66 hyperplastic polyps (HPs) by immunohistochemistry and gene mutation analysis. Histologically, 75% (9 of 12) of SSANs showed tubular or tubulovillous growth patterns rather than serrated ones in the HGD/intramucosal carcinoma component. All 5 SSANs with invasive carcinoma lost their serrated structure and developed increased extracellular mucin in their submucosal carcinoma component, a consistent feature of mucinous adenocarcinoma. Nuclear accumulations of ?-catenin and p53 were observed in 50% (6 of 12) and 41.7% (5 of 12) of SSANs, respectively, and were exclusively present in HGD/carcinoma areas. By contrast, neither nuclear ?-catenin nor p53 expressions were seen in HPs or SSAs (P<0.0001). BRAF mutations (V600E) were observed in 45.8% (11 of 24) of HPs, 60.9% (14 of 23) of SSAs, and 63.6% (7 of 11) of SSANs, and were equally found in both SSA and carcinoma/HGD areas of the individual SSANs. KRAS exon 1 mutations were uncommon in all 3 groups (4.2%, 4.4%, and 0%, respectively). No mutations of PIK3CA exon 9 or exon 20 were found in any cases that were examined. These findings suggest that BRAF mutations may be associated with the pathogenesis of SSA, but progression to HGD or early invasive carcinoma may be associated with other factors, such as alterations of p53 and ?-catenin. In addition, our histologic observations suggest a possible close association between SSAN and mucinous adenocarcinoma.
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Role for p16(INK4a) in progression of gastrointestinal stromal tumors of the stomach: alteration of p16(INK4a) network members.
Hum. Pathol.
PUBLISHED: 01-16-2011
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Gastrointestinal stromal tumors feature a wide spectrum of biologic behavior, ranging from benign to extremely malignant. To determine the role of p16(INK4a) alteration in progression of gastrointestinal stromal tumors of the stomach, we have investigated protein expression and gene methylation in correlation with clinicopathologic factors and survival. In addition to immunohistochemical analysis of p16(INK4a) in a series of 95 cases, real-time quantitative methylation specific polymerase chain reaction for p16(INK4a) and immunostaining for cyclin D1, cyclin E, pRb, DP-1, E2F-1, and Ki-67 were also evaluated in randomly selected samples. The p16(INK4a) labeling indices ranged from 0% to 74% (median, 21%), demonstrating a significant inverse correlation with size (P = .046). On univariate (P = .003) and multivariate (P = .067) analyses, loss of p16(INK4a) expression increased the likelihood of a poor tumor-related survival. In addition, size (P = .036) and the mitotic index (P = .005) had independent prognostic influence. The p16(INK4a) methylation index, which ranged from 0% to 100% (median, 17%), was significantly higher in larger tumors (P < .001) and in high-risk category lesions (P = .001) and inversely correlated with protein expression. Hierarchical cluster analysis based on expression of p16(INK4a) network members identified 2 clusters in 27 randomly selected tumor samples, containing 11 and 16 tumors each. Former cluster samples demonstrated higher risk category (P = .022), higher p16(INK4a) methylation (P < .001), and more reduced pRb expression (P < .018). In addition, p16(INK4a) network members clustered into 2 groups: (1) showing down-regulated p16(INK4a) protein and up-regulating of both cyclin D1 and DP-1 and (2) down-regulated pRb and up-regulated E2F-1. We conclude that p16(INK4a) alteration has an important role in progression of gastrointestinal stromal tumors of the stomach. Furthermore, the study provides a possible link between regulation of p16(INK4a) network members and gastrointestinal stromal tumors.
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Significance of dysadherin and E-cadherin expression in differentiated-type gastric carcinoma with submucosal invasion.
Hum. Pathol.
PUBLISHED: 01-15-2011
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Dysadherin is a cancer-associated cell membrane glycoprotein that down-regulates E-cadherin and plays important roles in tumor progression and metastasis. Differentiated-type gastric carcinoma can be classified into 2 histologic subtypes according to the presence of poorly differentiated components: a mixed type (differentiated carcinoma with poorly differentiated components) and a pure type (purely differentiated-type adenocarcinoma). We studied the clinicopathologic features of 318 cases of differentiated-type gastric carcinoma with submucosal invasion and evaluated the immunohistochemical expression of dysadherin and E-cadherin. We also evaluated 46 cases of metastatic lymph nodes. Tumors with combined dysadherin-positive (?50%) expression and E-cadherin-negative (<50%) expression had significantly higher proportions of the moderately differentiated type, deeper submucosal invasion, positivity of lymphatic permeation, and positivity of lymph node metastasis than tumors with other combinations of dysadherin and E-cadherin expression (P = .0009, P = .0015, P = .0273, and P = .0187, respectively). Moreover, the frequency of dysadherin-positive (?50%) expression was higher in the mixed type (60.3%) than in the pure type (12.4%) (P < .0001), whereas the frequency of E-cadherin-negative (<50%) expression was higher in the mixed type (84.5%) than in the pure type (50.5%) (P < .0001). The frequency of dysadherin expression in the metastatic lymph nodes (80.4%) was significantly higher than that in the primary tumors (45.7%) (P = .001). Dysadherin-positive (?50%) expression and E-cadherin-negative (<50%) expression may be correlated with the mixed type. Combined dysadherin-positive (?50%) expression and E-cadherin-negative (<50%) expression may be valuable information for predicting aggressive tumor behavior.
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A case of secondary malignant giant-cell tumor of bone with p53 mutation after long-term follow-up.
Hum. Pathol.
PUBLISHED: 01-14-2011
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A 46-year-old man was admitted to the hospital with a recurrent giant-cell tumor of the distal femur. This was his fourth recurrence, and it had occurred 16 years after his last treatment. The resected recurrent tumor was histologically determined to be a conventional giant-cell tumor. However, a single lung metastatic lesion and local recurrence were noticed 6 months after the resection, both of which were surgically excised. The lung lesion was histologically determined to be an implantation of giant-cell tumor, whereas the local recurrent lesion contained a clearly separated fibrosarcomatous area within the conventional giant-cell tumor. Immunohistochemistry showed diffuse and strong p53 expression in the fibrosarcomatous area. Direct sequencing revealed a p53 mutation in the sarcomatous area and a recessive mutant signal in the conventional area. The lung lesion also contained the same p53 mutation. Identification of the p53 mutation may help in diagnosing potential malignant transformation of giant-cell tumor.
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Ciliates promote the transfer of the gene encoding the extended-spectrum ?-lactamase CTX-M-27 between Escherichia coli strains.
J. Antimicrob. Chemother.
PUBLISHED: 12-21-2010
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The mechanism by which Escherichia coli acquires multidrug resistance genes from other bacteria in the natural environment or livestock is still unclear. The ability of ciliates to promote the transfer of genes encoding extended-spectrum ?-lactamases (ESBLs) between the CTX-M-27 donor and clinically isolated recipient E. coli strains was investigated.
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Host range of obligate intracellular bacterium Parachlamydia acanthamoebae.
Microbiol. Immunol.
PUBLISHED: 12-16-2010
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The obligate intracellular bacterium Parachlamydia acanthamoebae is a potential human pathogen, but the host range of the bacteria remains unknown. Hence, the growth of P. acanthamoebae Bn? in protozoa (Tetrahymena, Acanthamoeba, Dictyostelium) and mammalian cells (HEp-2, Vero, THP-1, PMA-stimulated THP-1, Jurkat) was assessed using an AIU assay which had been previously established by the current authors. P. acanthamoebae grew in Acanthamoeba but not in the other cell types. The growth was also confirmed using DAPI staining, FISH and TEM. These results indicate that the host range of P. acanthamoebae is limited.
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[Clinicopathological features of small intestinal tumors].
Gan To Kagaku Ryoho
PUBLISHED: 08-19-2010
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Small intestinal neoplasms are rare, accounting for only 1-2% of all gastrointestinal neoplasms. Variable neoplasms are recognized in the small intestine. Comparatively frequent malignant lesions are carcinoma, carcinoid tumor, malignant lymphoma, and GIST (gastrointestinal stromal tumor). The prognosis of small intestinal cancer is poor, because preoperative diagnosis is difficult and it is usually discovered at the advanced stage. In addition, it is thought that there are few small intestinal cancers of an adenoma origin, but dysplasia is considered to be associated with that complicated by Crohns disease. The incidence of carcinoid tumor is lower in Japan than in Western countries. Although it is often discovered at the advanced stage, its prognosis is relatively good in spite of the high incidence of metastasis because of its low-grade malignancy. Among malignant lymphomas of the small intestine, the incidence of MALT lymphoma is lower, and those of T cell and follicular ones are higher than in the stomach. Lymphomas with minimal cellular atypia are often encountered, and in such cases biopsy diagnosis is difficult. The prognosis of small intestinal lymphoma is better than for small intestinal cancer. It must be recalled that multiple GIST occurs in specific disorders such as von Recklinghausens disease and familial disease among small intestinal GIST, although very rarely. The prognosis of malignant small intestinal disease will improve through early diagnosis with the recent progress in the procedures for detecting small intestinal disease.
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Impact of free-living amoebae on presence of Parachlamydia acanthamoebae in the hospital environment and its survival in vitro without requirement for amoebae.
J. Clin. Microbiol.
PUBLISHED: 07-14-2010
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Parachlamydia acanthamoebae is an obligately intracellular bacterium that infects free-living amoebae and is a potential human pathogen in hospital-acquired pneumonia. We examined whether the presence of P. acanthamoebae is related to the presence of Acanthamoeba in an actual hospital environment and assessed the in vitro survival of P. acanthamoebae. Ninety smear samples were collected between November 2007 and March 2008 (trial 1, n = 52) and between October 2008 and February 2009 (trial 2, n = 38) from the floor (dry conditions, n = 56) and sink outlets (moist conditions, n = 34) of a hospital. The prevalences of P. acanthamoebae DNA in the first and second trials were 64.3% and 76%, respectively. The prevalences of Acanthamoeba DNA in the first and second trials were 48% and 63.1%, respectively. A statistical correlation between the prevalence of P. acanthamoebae and that of Acanthamoeba was found (trial 1, P = 0.011; trial 2, P = 0.022), and that correlation increased when samples from just the dry area (floor smear samples, P = 0.002) were analyzed but decreased when samples from a moist area were analyzed (P = 0.273). The in vitro experiment showed that, without Acanthamoeba, P. acanthamoebae could not survive in dry conditions for 3 days at 30 degrees C or 15 days at 15 degrees C. Thus, both organisms were coincidentally found in an actual hospital environment, with the presence of Acanthamoeba having a significant effect on the long-term survival of P. acanthamoebae, suggesting that this potential human pathogen could spread through a hospital environment via Acanthamoeba.
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Loss of heterozygosity on tuberous sclerosis complex genes in multifocal micronodular pneumocyte hyperplasia.
Mod. Pathol.
PUBLISHED: 06-04-2010
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Multifocal micronodular pneumocyte hyperplasia is a rare pulmonary manifestation of tuberous sclerosis complex (TSC) that is a tumor suppressor gene disorder characterized by many hamartomas. A purported mechanism of hamartomatous proliferation in TSC is constitutive activation of the mammalian target of rapamycin (mTOR) signaling pathway dysregulated by a functional loss of TSC genes. Although multifocal micronodular pneumocyte hyperplasia develops locally as self-limited, benign lesions, it is morphologically similar to the preinvasive lesion of pneumocytes that characterize atypical adenomatous hyperplasia or bronchioloalveolar carcinoma. Frequently both conditions include a loss of heterozygosity on TSC. The goal of this study was to determine whether multifocal micronodular pneumocyte hyperplasia is neoplastic. Loss of heterozygosity on TSC genes and immunohistochemistry for mTOR-related proteins (phospho-mTOR, phospho-p70S6K, phospho-S6, and phospho-Akt) were analyzed in 42 lesions: 16 multifocal micronodular pneumocyte hyperplasia (7 patients with TSC, 1 TSC not confirmed), 14 atypical adenomatous hyperplasia, and 12 bronchioloalveolar carcinoma (9 and 12 patients, respectively). The results showed that at least one of two multifocal micronodular pneumocyte hyperplasia lesions from each patient had loss of heterozygosity on TSC1 or TSC2 (15 or 50%) and were frequently immunopositive for phospho-mTOR (88%), phospho-p70S6K (100%), and phospho-S6 (100%) but not phospho-Akt (14%), an upstream regulatory protein of mTOR. Loss of heterozygosity of TSC was found in the preinvasive lesions of pneumocytes, equal to or less than multifocal micronodular pneumocyte hyperplasia. In contrast, phospho-Akt was expressed in the preinvasive lesions of pneumocytes more frequently than multifocal micronodular pneumocyte hyperplasia, but the other mTOR-related proteins were less frequently expressed in the former than in the latter. These outcomes suggest that functional loss of TSCs and consequent hyperphosphorylation of mTOR-related proteins in multifocal micronodular pneumocyte hyperplasia may cause its benign neoplastic proliferation of pneumocytes.
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Endosymbiotic bacterium Protochlamydia can survive in acanthamoebae following encystation.
Environ Microbiol Rep
PUBLISHED: 06-01-2010
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Obligate intracellular bacteria are commonly seen as endosymbionts of acanthamoebae. However, whether endosymbionts can survive amoebal encystations remains a significant challenge in cellular biology. The survival of the endosymbiotic bacteria Protochlamydia belonging to environmental chlamydiae found in an amoebal isolate that we have previously reported (Environmental Microbiology Reports, DOI: 10.1111/j.1758-2229.2009.00094.x, 2009) following encystation was therefore assessed. The bacteria were observed in cysts and trophozoites reverted from cysts by analysis with transmission electron microscope, and the bacterial 16S rRNA transcripts were detected in amoeba cultures following encystations by reverse transcription polymerase chain reaction method. Furthermore, the bacterial growth was also confirmed, by fluorescent in situ hybridization analysis and the AIU assay that we have previously established (Applied Environmental Microbiology, 74: 6397-6404, 2008), in trophozoites reverted from cysts stored at 4°C for up to a month after encystation. Thus, these results demonstrated that Protochlamydia could survive in acanthamoebae following encystation. Our findings suggest that amoeba cysts might be further studied in order to understand their role in the environmental survival of endosymbionts.
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Mucin core protein expression in serrated polyps of the large intestine.
Virchows Arch.
PUBLISHED: 05-05-2010
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Sessile serrated adenoma (SSA) has been proposed as a precursor to microsatellite-unstable colorectal carcinoma. However, histological criteria dictating how to differentiate serrated lesions have not been completely established, and a histological overlap exists between SSA and hyperplastic polyps (HPs), particularly the microvesicular type. In this study, based on a critical review of histology, we aimed to elucidate the potential utility of the mucin phenotype in the identification of SSA. We evaluated mucin core protein expression (MUC2, MUC5AC, and MUC6) by immunohistochemical stain in 65 cases of microvesicular-type HPs, 51 SSAs, and 72 traditional serrated adenomas (TSAs). SSAs had clinicopathological and morphological features distinct from those of HPs and TSAs. MUC6 was more frequently positive in SSAs (39%) than in TSAs (4%) and HPs (19%) (P?
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Evaluation of new subclassification of type V(I) pit pattern for determining the depth and type of invasion of colorectal neoplasm.
J. Gastroenterol.
PUBLISHED: 04-27-2010
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Colorectal neoplasms with a type V(I) pit pattern include various lesions, such as adenomas, intramucosal cancers, and submucosal carcinomas.
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[A case of stage IVb small cell carcinoma of the esophagus obtained prolonged survival after combined modality therapy].
Gan To Kagaku Ryoho
PUBLISHED: 04-24-2010
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Small cell carcinoma of the esophagus is a relatively rare disease, and its prognosis is quite poor, because of its rapid progression. A 76-year-old female visited our hospital with the complaint of a poor appetite. Upper gastrointestinal endoscopic examination(GIS)revealed an ulcerated lesion in the lower portion of the thoracic esophagus, and we diagnosed small cell carcinoma by a biopsy specimen. A computer tomography scan revealed solitary liver metastasis, and lymph node swelling on the left side of the superior mesenteric artery. So, we started chemotherapy with VP-16 and CDDP, according to a regimen for small cell carcinoma of the lung. After 4 courses of chemotherapy, the primary lesion, liver metastasis, and lymph node swelling had disappeared, so we decided it was a complete response. 20 months later, follow-up GIS revealed low elevated lesion at the margins of an ulcerated scar, and diagnosed squamous cell carcinoma by the biopsy specimen. The patient received 60 Gy radiotherapy in total, and is still alive 6 years after diagnosis without any evidence of recurrence.
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Gastric adenocarcinoma of fundic gland type (chief cell predominant type): proposal for a new entity of gastric adenocarcinoma.
Am. J. Surg. Pathol.
PUBLISHED: 04-23-2010
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Only a few cases of gastric adenocarcinoma of fundic gland type have been reported. Gastric adenocarcinoma with chief cell differentiation (GA-CCD) has been recently reported as a new variant of gastric adenocarcinoma. However, its clinicopathologic features are uncertain. To elucidate them, GA-CCDs exhibiting pepsinogen-I expression (10 lesions: Group A) and randomly selected gastric adenocarcinomas of differentiated type (111 lesions: Group B) were evaluated in this study. Cell differentiation by MUC2, MUC5AC, MUC6, CD10, pepsinogen-I, H+/K+-ATPase and chromogranin A, cell proliferation by Ki-67, and overexpression of p53 protein were evaluated immunohistochemically. In Group A, all GA-CCDs were located in the upper third of the stomach. Tumors were small, with the average maximum diameter ranging from 4 to 20 (average, 8.6) mm. Histologically, GA-CCDs were well-differentiated adenocarcinomas composed of pale gray-blue, basophilic columnar cells with mild nuclear atypia, resembling chief cells. Immunohistochemically, scattered positivity for H+/K+-ATPase was observed in addition to expression of pepsinogen-I and MUC6, indicating focal differentiation toward parietal cells. In Group B, pepsinogen-I was very focally expressed in 2 cases. As these 2 cases exhibited different clinicopathological and histologic features, they cannot be categorized as GA-CCD. Mild atypism, no lymphovascular invasion, low proliferative activity, no overexpression of p53, and no recurrence indicated less aggressiveness of GA-CCD. GA-CCD is rare, but it has distinct clinicopathological characteristics, especially in terms of tumor location, histologic features, phenotypic expression, and low-grade malignancy. We propose gastric adenocarcinoma of fundic gland type (chief cell predominant type) as a new entity of gastric adenocarcinoma.
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Stability of Chlamydophila pneumoniae in a harsh environment without a requirement for acanthamoebae.
Microbiol. Immunol.
PUBLISHED: 04-10-2010
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The effect of actual interactions between Chlamydophila pneumoniae and amoebae (Acanthamoeba) on the survival of C. pneumoniae was investigated. C. pneumoniae and amoebae were detected in 75 soil samples by IFU assay and PCR. Although C. pneumoniae could not be cultured, the DNA prevalence of C. pneumoniae and amoebae in natural soil was 20% and 92% (no correlation between the prevalence of DNA was observed). The viability of C. pneumoniae spiked in autoclaved soil was assessed by IFU assay and RT-PCR. Although the number of infective progeny decreased for three days, transcripts of C. pneumoniae were detected for up to 98 days independently of amoebae. The stability of C. pneumoniae in liquid medium was also assessed by IFU assay and transmission electron microscopy. The bacteria could survive at 15 degrees C for 14 days independently of amoebae. Bacteria cultured without amoebae were confirmed to have normal structures. Thus, the presence of amoebae has no effect on C. pneumoniae survival, and the bacteria can survive in the absence of host cells for an extended period of time.
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Ciliates rapidly enhance the frequency of conjugation between Escherichia coli strains through bacterial accumulation in vesicles.
Res. Microbiol.
PUBLISHED: 04-01-2010
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The mechanism underlying bacterial conjugation through protozoa was investigated. Kanamycin-resistant Escherichia coli SM10?+ carrying pRT733 with TnphoA was used as donor bacteria and introduced by conjugation into ciprofloxacin-resistant E. coli clinical isolate recipient bacteria. Equal amounts of donor and recipient bacteria were mixed together in the presence or absence of protozoa (ciliates, free-living amoebae, myxamoebae) in Pages amoeba saline for 24 h. Transconjugants were selected with Luria broth agar containing kanamycin and ciprofloxacin. The frequency of conjugation was estimated as the number of transconjugants for each recipient. Conjugation frequency in the presence of ciliates was estimated to be approximately 10??, but in the absence of ciliates, or in the presence of other protozoa, it was approximately 10??. Conjugation also occurred in culture of ciliates at least 2 h after incubation. Successful conjugation was confirmed by the polymerase chain reaction. Addition of cycloheximide or latrunculin B resulted in suppression of conjugation. Heat killing the ciliates or bacteria had no effect on conjugation frequency. Co-localization of green fluorescent protein-expressing E. coli and PKH-67-vital-stained E. coli was observed in the same ciliate vesicles, suggesting that both donor and recipient bacteria had accumulated in the same vesicle. In this study, the conjugation frequency of bacteria was found to be significantly higher in vesicles purified from ciliates than those in culture suspension. We conclude that ciliates rapidly enhance the conjugation of E. coli strains through bacterial accumulation in vesicles.
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