JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Intraductal carcinoma of the prostate: interobserver reproducibility survey of 39 urologic pathologists.
Ann Diagn Pathol
PUBLISHED: 08-26-2014
Show Abstract
Hide Abstract
The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, ?(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.
Related JoVE Video
Rhabdoid differentiation is associated with aggressive behavior in renal cell carcinoma: a clinicopathologic analysis of 76 cases with clinical follow-up.
Am. J. Surg. Pathol.
PUBLISHED: 08-16-2014
Show Abstract
Hide Abstract
Rhabdoid differentiation has been associated with aggressive behavior in carcinomas from different organ systems. A recent consensus statement of the International Society of Urological Pathology (ISUP), in addition to proposing a nucleolar grading system (ISUP grade) for renal cell carcinoma (RCC) to replace the Fuhrman system, recommended reporting the presence of rhabdoid differentiation in RCC and considering tumors with rhabdoid differentiation to be ISUP grade 4. Although it has been shown that rhabdoid differentiation is associated with increased grade and stage of RCC, it has not been fully demonstrated whether it has an adverse effect independent of this association with increased grade and stage. We provide the largest clinicopathologic analysis of RCC with rhabdoid differentiation to date (76 cases), including characterization of metastatic disease. In addition, by constructing a multivariable model including tumor grade, stage, necrosis, and distant metastasis to compare a series of 49 clear cell RCC with rhabdoid differentiation with a cohort of 41 clear cell RCCs without rhabdoid differentiation, we demonstrate that the presence of rhabdoid differentiation in clear cell RCC confers an increased risk of death (hazard ratio=5.25; 95% confidence interval, 2.1-14.3) independent of these other adverse prognostic factors. These findings underscore the significance of rhabdoid differentiation in RCC as an adverse prognostic factor and support the recent reporting and grading recommendations of the ISUP.
Related JoVE Video
Tuberous Sclerosis-associated Renal Cell Carcinoma: A Clinicopathologic Study of 57 Separate Carcinomas in 18 Patients.
Am. J. Surg. Pathol.
PUBLISHED: 08-06-2014
Show Abstract
Hide Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with characteristic tumors involving multiple organ systems. Whereas renal angiomyolipoma (AML) is common in TSC, renal cell carcinoma (RCC) is rarely reported. Fifty-seven RCCs from 13 female and 5 male TSC patients were reviewed. Age at surgery ranged from 7 to 65 years (mean: 42 y). Nine patients (50%) had multiple synchronous and/or metachronous RCCs (range of 2 to 20 RCCs) and 5 had bilateral RCCs (28%). Seventeen patients (94%) had histologically confirmed concurrent renal AMLs, including 15 with multiple AMLs (88%) and 9 (50%) with AMLs with epithelial cysts. None of the 15 patients with available clinical follow-up information had evidence of distant metastatic disease from 6 to 198 months after their initial surgery (mean: 52 mo). The 57 RCCs exhibited 3 major distinct morphologies: (1) 17 RCCs (30%) had features similar to tumors previously described as "renal angiomyoadenomatous tumor" or "RCC with smooth muscle stroma"; (2) 34 RCCs (59%) showed features similar to chromophobe RCC; and (3) 6 RCCs (11%) showed a granular eosinophilic-macrocystic morphology. Distinct histologic changes were also commonly present in the background kidney parenchyma and included cysts or renal tubules lined by epithelial cells with prominent eosinophilic cytoplasm, nucleomegaly, and nucleoli. Immunohistochemically, all RCCs tested showed strong nuclear reactivity for PAX8 and HMB45 negativity. Compared with sporadic RCCs, TSC-associated RCCs have unique clinicopathologic features including female predominance, younger age at diagnosis, multiplicity, association with AMLs, 3 recurring histologic patterns, and an indolent clinical course. Awareness of the morphologic and clinicopathologic spectrum of RCC in this setting will allow surgical pathologists to better recognize clinically unsuspected TSC patients.
Related JoVE Video
Does cumulative prostate cancer length in prostate biopsies improve prediction of clinically insignificant cancer at radical prostatectomy in patients eligible for active surveillance?
BJU Int.
PUBLISHED: 07-18-2014
Show Abstract
Hide Abstract
To evaluate if cumulative cancer length on prostate needle biopsy (Bx) divided by the number of biopsy cores (CCL/core) could improve prediction of insignificant cancer (IC) on radical prostatectomy (RP) in patients with prostate cancer (PCA) eligible for active surveillance (AS).
Related JoVE Video
Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies.
J. Urol.
PUBLISHED: 04-10-2014
Show Abstract
Hide Abstract
The DOCUMENT multicenter trial in the United States validated the performance of an epigenetic test as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. Confirming an increased negative predictive value could help avoid unnecessary repeat biopsies.
Related JoVE Video
Epithelial-to-mesenchymal transition in renal neoplasms.
Adv Anat Pathol
PUBLISHED: 04-10-2014
Show Abstract
Hide Abstract
Epithelial-to-mesenchymal transition (EMT) describes a phenotypical change induced in epithelial cells that lose their cell-cell basement membrane contacts and their structural polarity to become spindle-shaped and morphologically similar to mesenchymal/myofibroblast cell. The abnormal induction of EMT has been demonstrated to contribute to cancer dissemination and progression. Renal cell carcinoma (RCC) with sarcomatoid differentiation (sarcomatoid RCC) represents a good example of EMT both morphologically and immunohistochemically. Early spindle cell changes can at times be identified in RCC and likely represent an early step toward EMT. Herein, we present a review of the current understanding of EMT in renal neoplasms including some known signaling regulation, the association of sarcomatoid differentiation in RCC with aggressive behavior and dismal prognosis, and EMT-related tumor biology in sarcomatoid RCC. A better perception of the EMT may contribute toward an improved understanding of the development of sarcomatoid RCC. In addition, a distinct signature for sarcomatoid RCC may have utility in the differential diagnosis for prognostic stratification as well as in identifying novel genes and pathway targets for therapeutic intervention.
Related JoVE Video
Autophagic flux determines cell death and survival in response to Apo2L/TRAIL (dulanermin).
Mol. Cancer
PUBLISHED: 03-17-2014
Show Abstract
Hide Abstract
Macroautophagy is a catabolic process that can mediate cell death or survival. Apo2 ligand (Apo2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment (TR) is known to induce autophagy. Here we investigated whether SQSTM1/p62 (p62) overexpression, as a marker of autophagic flux, was related to aggressiveness of human prostate cancer (PCa) and whether autophagy regulated the treatment response in sensitive but not resistant PCa cell lines.
Related JoVE Video
Diagnostic criteria for ductal adenocarcinoma of the prostate: interobserver variability among 20 expert uropathologists.
Histopathology
PUBLISHED: 01-23-2014
Show Abstract
Hide Abstract
Ductal adenocarcinoma of the prostate (DAC) is clinically important, because its behaviour may differ from that of acinar adenocarcinoma. Our aims were to investigate the interobserver variability of this diagnosis among experts in uropathology and to define diagnostic criteria.
Related JoVE Video
Dysregulated D-Dopachrome Tautomerase, a Hypoxia Inducible Factor-Dependent Gene, Cooperates with Macrophage Migration Inhibitory Factor in Renal Tumorigenesis.
J. Biol. Chem.
PUBLISHED: 12-19-2013
Show Abstract
Hide Abstract
Clear cell renal cell carcinomas (ccRCC) are characterized by biallelic loss of the von Hippel Lindau tumor suppressor and subsequent constitutive activation of the hypoxia inducible factors, whose transcriptional programs dictate major phenotypic attributes of kidney tumors. We recently described a role for macrophage migration inhibitory factor (MIF) in ccRCC as an autocrine-signaling molecule with elevated expression in tumor tissues and in the circulation of patients that has potent tumor-cell survival effects. MIF is a pleiotropic cytokine implicated in a variety of diseases and cancers, and is the target of both small molecule and antibody-based therapies currently in clinical trials. Recent work by others has described D-dopachrome tautomerase (DDT) as a functional homologue of MIF with similar genomic structure and expression patterns. We thus sought to determine a role for DDT in renal cancer. We find that DDT expression mirrors MIF expression in ccRCC tumor sections with high correlation, and that mechanistically DDT is a novel hypoxia inducible gene and direct target of HIF1? and HIF2?. Functionally, DDT and MIF demonstrate significant overlap in controlling cell survival, tumor formation, and tumor- and endothelial-cell migration. However, DDT inhibition consistently displayed more severe effects on most phenotypes. Accordingly, while dual inhibition of DDT and MIF demonstrated additive effects in vitro; DDT plays a dominant role in tumor growth in vivo. Together our findings identify DDT as a functionally redundant but more potent cytokine to MIF in cancer, and suggest that current attempts to inhibit MIF signaling may fail due to DDT compensation.
Related JoVE Video
ERG protein expression as a biomarker of prostate cancer.
Biomark Med
PUBLISHED: 11-26-2013
Show Abstract
Hide Abstract
TMPRSS2-ERG is a recurrent rearrangement specific for prostate cancer, leading to the overexpression of a truncated ERG protein product that is amenable to immunohistochemical detection. Two monoclonal anti-ERG antibodies have currently been validated, with comparable sensitivity and specificity for detecting ERG rearrangement. ERG immunostaining has been applied in different settings to elucidate the role of ERG rearrangement and overexpression in prostate cancer tumorigenesis and progression, as well as to investigate potential diagnostic and prognostic applications. In this article we review the literature on the topic and suggest potential future applications.
Related JoVE Video
The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters.
Am. J. Surg. Pathol.
PUBLISHED: 09-13-2013
Show Abstract
Hide Abstract
The International Society of Urological Pathology 2012 Consensus Conference made recommendations regarding classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. Issues relating to prognostic factors were coordinated by a workgroup who identified tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading, and microvascular invasion as potential prognostic parameters. There was consensus that the main morphotypes of renal cell carcinoma (RCC) were of prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided additional prognostic information, and that clear cell tubulopapillary RCC was associated with a more favorable outcome. For tumors showing sarcomatoid or rhabdoid differentiation, there was consensus that a minimum proportion of tumor was not required for diagnostic purposes. It was also agreed upon that the underlying subtype of carcinoma should be reported. For sarcomatoid carcinoma, it was further agreed upon that if the underlying carcinoma subtype was absent the tumor should be classified as a grade 4 unclassified carcinoma with a sarcomatoid component. Tumor necrosis was considered to have prognostic significance, with assessment based on macroscopic and microscopic examination of the tumor. It was recommended that for clear cell RCC the amount of necrosis should be quantified. There was consensus that nucleolar prominence defined grades 1 to 3 of clear cell and papillary RCCs, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed upon that chromophobe RCC should not be graded. There was consensus that microvascular invasion should not be included as a staging criterion for RCC.
Related JoVE Video
Hereditary syndromes with associated renal neoplasia: a practical guide to histologic recognition in renal tumor resection specimens.
Adv Anat Pathol
PUBLISHED: 06-12-2013
Show Abstract
Hide Abstract
Many hereditary tumor syndromes are associated with neoplasms of the kidney. It is becoming increasingly well recognized that a given familial tumor syndrome may be very heterogenous in clinical appearance and that unrecognized patients may present initially for the treatment of a renal mass. It is therefore important for surgical pathologists to be aware of the specific gross and microscopic findings in the kidney that suggest a possible syndromic association. In this review, we detail the histologic features of syndromic-associated renal neoplasms, describe the presence of characteristic changes in the background renal parenchyma, and provide an update on associated extrarenal manifestations for each of the following syndromes: von Hippel-Lindau disease, hereditary papillary renal cell carcinoma (RCC), hereditary leiomyomatosis-RCC, Birt-Hogg-Dubé syndrome, tuberous sclerosis complex, germline succinate dehydrogenase mutation, hereditary nonpolyposis colorectal cancer syndrome, hyperparathyroidism-jaw tumor syndrome, PTEN hamartoma syndrome, constitutional chromosome 3 translocation, and familial nonsyndromic clear cell RCC. We also include a synopsis of renal medullary carcinoma because of its association with hereditary hemoglobinopathies.
Related JoVE Video
Analytical validation of the Oncotype DX prostate cancer assay - a clinical RT-PCR assay optimized for prostate needle biopsies.
BMC Genomics
PUBLISHED: 05-10-2013
Show Abstract
Hide Abstract
The Oncotype DX Prostate Cancer Assay is a multi-gene RT-PCR expression assay that was developed for use with fixed paraffin-embedded (FPE) diagnostic prostate needle biopsies containing as little as 1 mm of prostate tumor in the greatest dimension. The assay measures expression of 12 cancer-related genes representing four biological pathways and 5 reference genes which are algorithmically combined to calculate the Genomic Prostate Score (GPS). This biopsy-based assay has been analytically and subsequently clinically validated as a predictor of aggressive prostate cancer. The aim of this study was to validate the analytical performance of the Oncotype DX Prostate Cancer Assay using predefined acceptance criteria.
Related JoVE Video
Incidence and clinicopathological characteristics of intraductal carcinoma detected in prostate biopsies: a prospective cohort study.
Histopathology
PUBLISHED: 03-13-2013
Show Abstract
Hide Abstract
Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathological entity and is associated with aggressive, high-grade and high-volume prostate carcinoma (PCa). The incidence, clinicopathological characteristics and prognostic significance of IDC-P have not been reported in prostate biopsies (PBx) that surgical pathologists encounter in their daily practice.
Related JoVE Video
Robotic real-time near infrared targeted fluorescence imaging in a murine model of prostate cancer: a feasibility study.
Urology
PUBLISHED: 02-05-2013
Show Abstract
Hide Abstract
To evaluate the detection of near-infrared fluorescence from prostate tumors stained with a prostate-specific membrane antigen (PSMA)-targeted tracer developed in our institution with a novel robotic imaging system.
Related JoVE Video
Metanephric adenoma and solid variant of papillary renal cell carcinoma: common and distinctive features.
Histopathology
PUBLISHED: 01-31-2013
Show Abstract
Hide Abstract
To evaluate morphological and immunohistochemical (IHC) features helpful in distinguishing metanephric adenoma (MA) from solid papillary renal cell carcinoma (s-PRCC).
Related JoVE Video
Prostate cancer patients older than 70 years treated by radical prostatectomy have higher biochemical recurrence rate than their matched younger counterpart.
Prostate
PUBLISHED: 01-03-2013
Show Abstract
Hide Abstract
Consensus on prostate cancer (PCA) treatment in older men is currently lacking. We evaluated clinicopathological and oncological outcomes in patients >70-year-old treated with radical prostatectomy (RP).
Related JoVE Video
PAX8 and PAX2 immunostaining facilitates the diagnosis of primary epithelial neoplasms of the male genital tract.
Am. J. Surg. Pathol.
PUBLISHED: 09-22-2011
Show Abstract
Hide Abstract
PAX8 and PAX2 are cell-lineage-specific transcription factors that are essential for the development of Wolffian and Müllerian ducts and have recently emerged as specific diagnostic markers for tumors of renal or Müllerian origin. Little is known about their expression in the Wolffian duct-derived human male genital tract. We report our findings of PAX8 and PAX2 expression in the epithelium of the normal male genital tract and in epithelial tumors derived therefrom using immunohistochemistry (IHC). We found that PAX8 and PAX2 were expressed in the epithelium of the male genital tract from the rete testis to the ejaculatory duct. Rare glands in the prostatic central zone, a tissue of purported Wolffian duct origin, were focally positive for PAX2, but no PAX8 was detected in this area, a finding that may warrant further study. We found diffuse expression of PAX8 and PAX2 in 1 case each of serous cystadenoma of the epididymis, carcinoma of the rete testis, Wolffian adnexal tumor of the seminal vesicle, and endometrioid carcinoma of the seminal vesicle. Neither PAX8 nor PAX2 was detected in the seminiferous tubules and interstitium of the normal testis, nor in Leydig cell tumors (n=6), Sertoli cell tumors (n=2), or 48 of 49 germ cell tumors. One pediatric yolk sac tumor showed focal and weak staining for PAX8. Tumors of mesothelial origin, that is, adenomatoid tumors (n=3) and peritoneal malignant mesotheliomas (n=37) in men, were negative for PAX2 and PAX8. Neither PAX2 nor PAX8 was present in other areas of the prostate. Expression of PAX8 and PAX2 in these primary epithelial neoplasms of the male genital tract is due to their histogenetic relationship with Wolffian or Müllerian ducts. PAX8 and PAX2 IHC may facilitate the diagnosis of these tumors and should be included in the differential diagnostic IHC panel.
Related JoVE Video
Discrepancy in prostate cancer localization between biopsy and prostatectomy specimens in patients with unilateral positive biopsy: implications for focal therapy.
Prostate
PUBLISHED: 08-18-2011
Show Abstract
Hide Abstract
Unilateral ablative strategy success depends on reliable prediction of prostate cancer (PCA) location. We evaluated the discrepancy in PCA localization between unilateral positive biopsy (PBx) and radical prostatectomy (RP).
Related JoVE Video
Folate hydrolase (prostate-specific membrane [corrected] antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature.
Mod. Pathol.
PUBLISHED: 07-01-2011
Show Abstract
Hide Abstract
Folate hydrolase (prostate-specific antigen) 1 (FH(PSA)1), also known as prostate-specific membrane antigen (PSMA), is a transmembrane receptor expressed on prostate cancer cells that correlates with a more aggressive phenotype. Recent studies have demonstrated FH(PSA)1 expression in numerous benign and malignant tissue types, as well as the malignant neovasculature. As FH(PSA)1 represents a diagnostic immunomarker for prostate cancer, we explored its expression pattern in various subtypes of bladder cancer. Immunohistochemical analysis (IHC) of FH(PSA)1 was performed using tissue microarrays constructed from 167 bladder cancers, including 96 urothelial carcinomas (UCCs), 37 squamous cell carcinomas, 17 adenocarcinomas and 17 small cell carcinomas. We used a FH(PSA)1 monoclonal antibody obtained from Dako (clone 3E6, dilution 1:100), which recognizes the epitope present in the 57-134 amino acid region of the extracellular portion of the PSMA molecule. Intensity of IHC staining was scored as 0 (no expression) to 3+ (strong expression), with 2-3+ IHC considered a positive result. FH(PSA)1 demonstrated expression in a subset of bladder cancers and was most common in small cell carcinoma (3/17; 18%), with concurrent expression in non-small cell components in a subset of cases (2/6). FH(PSA)1 expression was less frequent in UCC (3/96; 3%) and adenocarcinoma (2/17; 12%). None of the squamous cell carcinomas demonstrated tumor cell expression of FH(PSA)1. However, all bladder cancers examined expressed FH(PSA)1 in the tumor vasculature, suggesting a potential role for this molecule in mediating new vessel ingrowth. FH(PSA)1 may occasionally be expressed in various subtypes of bladder cancer. These findings suggest cautious use of FH(PSA)1 as a diagnostic marker for prostatic tissue invading the bladder. The finding of FH(PSA)1 in the bladder cancer neovasculature suggests that this molecule may promote tumor growth and may represent a potential new vascular target in this disease.
Related JoVE Video
Grading of clear cell renal cell carcinoma should be based on nucleolar prominence.
Am. J. Surg. Pathol.
PUBLISHED: 07-01-2011
Show Abstract
Hide Abstract
Fuhrman grading of renal cell carcinoma focuses on features of nuclear size, nuclear shape, and nucleolar prominence. Despite the reported widespread usage of Fuhrman grading in clinical studies, there is debate as to the prognostic significance and reproducibility of its criteria. It has been noted that many pathologists rely on assessment of nucleolar prominence alone when grading renal cell carcinoma; however, the validity of this remains unconfirmed. This study was undertaken to determine the relationship of the 3 morphologic components of the Fuhrman grading system with one another and to determine which, if any of these, can be correlated with outcome for clear cell renal cell carcinoma. One hundred twenty-one organ-confined clear cell renal cell carcinomas were examined in this study. Parameters of nuclear size (area, major axis, perimeter) and nuclear shape (shape factor, nuclear compactness) were assessed by image analysis, whereas nucleolar prominence was assigned (grades 1 to 3) using the criteria of Fuhrman. On the basis of the predominant grade present, there were 17 nucleolar grade 1, 90 nucleolar grade 2, and 14 nucleolar grade 3 tumors. When the high-power field in each tumor with the worst nucleolar grade was assessed, there was 1 nucleolar grade 1, 68 nucleolar grade 2, and 52 nucleolar grade 3 tumors. Predominant and worst nucleolar grade correlated with all measures of nuclear size, but not nuclear shape. Worst nucleolar grade and all parameters of nuclear size were significantly associated with outcome. On multivariate analysis, worst nucleolar grade retained a significant association with survival when modeled with nuclear area. Neither worst nucleolar grade nor major nuclear axis/nuclear perimeter was significantly associated with survival when modeled together. In this study, we have shown that worst nucleolar grade and nuclear size are of prognostic significance for clear cell renal cell carcinoma. We have further shown the association of worst nucleolar grade with outcome to be independent of nuclear area, whereas it is a dependent variable when tested against other parameters of nuclear size. These findings indicate that worst nucleolar grading alone is a valid grading parameter for clear cell renal cell carcinoma.
Related JoVE Video
The utility of ERG/P63 double immunohistochemical staining in the diagnosis of limited cancer in prostate needle biopsies.
Am. J. Surg. Pathol.
PUBLISHED: 05-31-2011
Show Abstract
Hide Abstract
Diagnosis of limited cancer can be challenging in prostate needle biopsies, and immunohistochemistry is commonly used in such settings. Recently, TMPRSS2:ERG gene rearrangement was found to be highly specific for and detected in approximately 50% of prostate cancer. Positive immunohistochemical staining with a novel anti-ERG antibody highly correlated with TMPRSS2:ERG gene rearrangement status. We developed a double immunohistochemical staining containing both erythroblastosis virus E26 oncogen (ERG) and basal cell marker P63 antibodies and evaluated its use in the diagnosis of limited cancer in prostate needle biopsies. A total of 77 prostate needle biopsies containing cancer occupying <1 mm of the length of only 1 core of the entire biopsy set were stained with the double stain containing ERG and P63 antibodies. ERG positivity and its staining intensity in cancerous and other noncancerous lesions were evaluated. ERG expression was detected in 42% (32 of 77) of cases, with strong, moderate, and weak staining intensity in 72%, 16%, and 12% of cases. The staining was uniform in 84% of cases and heterogeneous in 16% of cases with different staining intensities in >10% of cancerous cells. High-grade prostatic intraepithelial neoplasia was present in 17 cases, and in 5 (29%) cases ERG was positive in high-grade prostatic intraepithelial neoplasia glands, which were all immediately adjacent to or intermingled with ERG-positive cancerous glands. In 4 additional cases, positive ERG staining was found in morphologically benign glands, which were also immediately adjacent to or intermingled with ERG-positive cancerous glands. All other benign lesions distant from cancerous glands, including simple and partial atrophy, were negative for ERG. P63 was negative in all cancerous glands and positive in noncancerous lesions. The P63/ERG double immunostain combines the high sensitivity of P63 and the high specificity of ERG and may be potentially useful in the work-up of difficult prostate biopsies. The high specificity of ERG for the presence of cancer may have important implications for prostate biopsy interpretation and needs to be further validated in larger prospective studies.
Related JoVE Video
The diagnostic utility of novel immunohistochemical marker ERG in the workup of prostate biopsies with "atypical glands suspicious for cancer".
Am. J. Surg. Pathol.
PUBLISHED: 03-09-2011
Show Abstract
Hide Abstract
A diagnosis of "atypical glands suspicious for cancer" (ATYP) in prostate needle biopsy is associated with a 40% to 50% risk of finding prostate carcinoma (PCa) in subsequent biopsies. Many studies have attempted to identify clinical, histologic, or molecular characteristics of ATYP that correlated with the risk of PCa in follow-up biopsies. TMPRSS2:ERG gene rearrangement is the most common chromosomal alteration and is highly specific for PCa. Recently, 2 studies reported that positive immunohistochemical (IHC) stains with an ERG antibody highly correlated with the TMPRSS2:ERG gene rearrangement status. We evaluated the use of this antibody as an IHC marker on prostate biopsies with an initial ATYP diagnosis to determine whether positive ERG IHC was associated with increased PCa detection in subsequent biopsies, which therefore might be useful for stratifying ATYP prostate biopsies. ERG IHC was performed on 103 biopsies with initial ATYP diagnosis. Positive ERG IHC staining was detected in 16 of the 103 cases (15.5%) of the ATYP prostate biopsies. Of these 16 ERG-positive cases, the atypical glands were positive for ERG in 9 cases. In the remaining 7 cases, positive ERG staining was found in glands other than ATYP glands, including high-grade prostatic intraepithelial neoplasia and morphologically benign glands. ERG IHC was negative in other benign prostate lesions, including simple atrophy, partial atrophy, proliferative inflammatory atrophy, basal cell hyperplasia, postatrophic hyperplasia, and squamous metaplasia. In subsequent follow-up biopsies, PCa was detected in 7 of the 16 (43.8%) ERG-positive cases and in 42 of the 87 (48.3%) ERG-negative cases (P=0.952 by ? test). In biopsies with ERG-positive ATYP glands, cancer was found in 5 of 9 (55.6%) cases in subsequent biopsies. This is the first study to investigate the use of ERG IHC in difficult prostate biopsies. ERG IHC was positive in a small percentage (15.5%) of the ATYP prostate biopsies, and positive ERG staining did not correlate with the increased cancer detection in subsequent prostate biopsies. Therefore, ERG IHC is not useful for stratifying ATYP prostate biopsies to identify patients who have increased risk for PCa in repeat biopsies. Furthermore, positive ERG staining is not entirely specific for PCa and can occasionally be found in high-grade prostatic intraepithelial neoplasia and benign glands that are not associated with PCa in prostate biopsies.
Related JoVE Video
ERG gene rearrangement status in prostate cancer detected by immunohistochemistry.
Virchows Arch.
PUBLISHED: 03-07-2011
Show Abstract
Hide Abstract
TMPRSS2-ERG, the most common gene fusion in prostate cancer, is associated with expression of a truncated protein product of the oncogene ERG. A novel anti-ERG monoclonal antibody has been recently characterized. We investigated the correlation between ERG rearrangement assessed by fluorescence in situ hybridization (FISH) and ERG expression detected by immunohistochemistry in a large cohort of patients treated with radical prostatectomy for clinically localized prostate cancer. Thirteen tissue microarrays comprising 305 tumors and a subset of 112 samples of nonneoplastic prostatic tissue were assessed for ERG rearrangement status by FISH and for ERG expression by immunohistochemistry. Accuracy of ERG detection by immunohistochemistry in predicting ERG status as assessed by FISH (criterion standard) was calculated in terms of sensitivity, specificity, positive and negative predictive values. Of 305 tumor foci, 103 (34%) showed ERG rearrangement by FISH. ERG was detected by immunohistochemistry in 100 (33%) cases, 99 of which were FISH positive. ERG detection by immunohistochemistry demonstrated a sensitivity and specificity of 96% and 99%, respectively, with positive and negative predictive values of 99% and 98%, respectively. None of the 112 samples of nonneoplastic prostatic tissue was rearranged by FISH or showed any ERG expression. In conclusion, ERG detection by immunohistochemistry in prostate cancer was highly predictive of ERG rearrangement as assessed by FISH in a large cohort of prostatectomy patients. Given the high yield and the easier task of performing immunohistochemistry vs. FISH, ERG assessment by immunohistochemistry may be useful for characterizing ERG status in prostate cancer.
Related JoVE Video
Prostate cancer staging and grading at radical prostatectomy over time.
Adv Anat Pathol
PUBLISHED: 02-18-2011
Show Abstract
Hide Abstract
Prostate-specific antigen (PSA) testing has been associated with a sharp increase in prostate cancer (PCA) detection after its introduction in the late 1980s. Since its launch and its implementation as diagnostic test in 1994, temporal patterns in patients age and serum PSA level at presentation have changed, with younger patients being diagnosed at lower PSA cutoff levels. Many studies suggest that PSA screening has resulted in a profound downward migration in clinical and pathologic stage of newly diagnosed PCA, although the effect has slowed in the most recent years. The impact on tumor grading is less clear. Histologic grading of PCA, based on the Gleason system, is predictive of the biological behavior and prognosis of the tumor. If tumor progresses from low grade to high grade, the early detection would lead to a higher percentage of low-grade disease diagnosed over time. However, published data suggest that tumor grade shifts have occurred over time and are unlikely to be attributable to changes in tumor biology, but rather to changes in practice with respect to Gleason grading. This review will address PCA staging and grading trends from the pre-PSA era to the present time with emphasis on the potential role played by changes in clinical and pathologic practice.
Related JoVE Video
Renal cell carcinomas with intratumoral fat and concomitant angiomyolipoma: potential pitfalls in staging and diagnosis.
Am. J. Clin. Pathol.
PUBLISHED: 10-21-2010
Show Abstract
Hide Abstract
Intratumoral fat and angiomyolipomas (AMLs) occurring within renal cell carcinomas (RCCs) have rarely been reported but may be mistaken for tumor invasion into perinephric or renal sinus fat or misdiagnosed as tumor exhibiting sarcomatoid differentiation. We report 16 such cases. In 14 RCC cases, there was intratumoral fat, 9 of which had fat located peripherally near the capsule (n = 6), renal sinus (n = 1), or both (n = 2). Inflammatory infiltrates and osseous metaplasia were identified in the intratumoral fat in 7 and 8 cases, respectively. Two cases had intratumoral AML foci located at the periphery of RCC. Intratumoral fat or AML at the periphery of RCC simulated the invasion into the fat, while the smooth muscle component of AML resembled spindle cell, or sarcomatoid, differentiation. Our study highlights the potential pitfalls in staging and diagnosis when intratumoral fat or AML is found within RCC.
Related JoVE Video
Clear cell tubulopapillary renal cell carcinoma: a study of 36 distinctive low-grade epithelial tumors of the kidney.
Am. J. Surg. Pathol.
PUBLISHED: 10-07-2010
Show Abstract
Hide Abstract
Recently several low-grade renal cell tumors, distinct from those recognized by the 2004 World Health Organization classification of renal tumors, have been described. These tumors had similar clinicopathologic features, being low-stage tumors with cystic, tubuloacinar, and/or papillary architecture. The tumor cells were low grade with variable amounts of clear cytoplasm that was positive for cytokeratin 7 (CK7), but negative for CD10. Genetic changes characteristic of clear cell or papillary renal cell carcinoma were not seen in these tumors. We investigated the morphologic, immunohistochemical, and genetic features of 36 additional tumors. Immunohistochemistry was carried out for CK7, carbonic anhydrase 9, ?-methylacyl-CoA racemase, CD10, TFE-3, and desmin. Interphase fluorescence in situ hybridization was carried out with centromeric probes for chromosomes 3, 7, 17, and a subtelomeric probe for 3p25. Sequencing of von Hippel-Lindau gene and analysis of the methylation status of the promoter region was also carried out in 2 tumors. Thirty-six tumors from 33 patients (mean age: 60.4?, range: 26 to 88; 17 men and 16 women) were studied. Three patients had bilateral tumors and 1 patient had von Hippel-Lindau disease. Follow-up was available in 60% (20/33) of the patients for a mean of 27.4 (range 1 to 85) months. No patient had evidence of the disease after surgery except for the patient with von Hippel-Lindau disease, who was alive with stable disease in the contralateral kidney. All 36 tumors were small (mean size 2.4?cm; range 0.9 to 4.5?cm) and low stage (pT1). The majority was cystic and had prominent fibrous capsule and stroma. The tumors were composed of variable amount of cysts, papillae, tubules, acini, and solid nests. The most characteristic histologic features were branching tubules and acini and anastomosing clear cell ribbons with low-grade nuclei. All tumors were strongly positive for CK7 and variably positive for CA9, but largely negative for CD10, and negative for ?-methylacyl-CoA racemase and TFE-3. All but 1 tumor had no gains of chromosomes 7 and 17 and deletion of 3p. Only 1 tumor had low copy number gains of chromosomes 7 and 17. VHL gene mutation and promoter methylation were negative in 2 tumors analyzed. We show that these tumors, which we term as "clear cell tubulopapillary renal cell carcinoma," constitute a unique subtype in the spectrum of renal epithelial neoplasia based on their characteristic morphologic and immunohistochemical features.
Related JoVE Video
International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 3: extraprostatic extension, lymphovascular invasion and locally advanced disease.
Mod. Pathol.
PUBLISHED: 08-27-2010
Show Abstract
Hide Abstract
The International Society of Urological Pathology Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to extraprostatic extension (pT3a disease), bladder neck invasion, lymphovascular invasion and the definition of pT4 were coordinated by working group 3. It was agreed that prostate cancer can be categorized as pT3a in the absence of adipose tissue involvement when cancer bulges beyond the contour of the gland or beyond the condensed smooth muscle of the prostate at posterior and posterolateral sites. Extraprostatic extension can also be identified anteriorly. It was agreed that the location of extraprostatic extension should be reported. Although there was consensus that the amount of extraprostatic extension should be quantitated, there was no agreement as to which method of quantitation should be employed. There was overwhelming consensus that microscopic urinary bladder neck invasion by carcinoma should be reported as stage pT3a and that lymphovascular invasion by carcinoma should be reported. It is recommended that these elements are considered in the development of practice guidelines and in the daily practice of urological surgical pathology.
Related JoVE Video
ERG rearrangement is present in a subset of transition zone prostatic tumors.
Mod. Pathol.
PUBLISHED: 08-06-2010
Show Abstract
Hide Abstract
A majority of prostate cancers exhibit a recurrent gene rearrangement involving chromosome 21. In approximately 90% of cases, the rearrangement is characterized by fusion of the androgen-regulated gene TMPRSS2 with the oncogene ERG. A recent study suggested that TMPRSS2-ERG gene fusion is lacking in cancers arising from the transition zone of the prostate. A dominant transition zone cancer was detected in 62/397 (16%) patients who underwent radical prostatectomy at our institution and were reviewed and mapped by a single pathologist. In 46/62 specimens, a secondary tumor was identified in the peripheral zone of the prostate. A tissue microarray containing both transition and peripheral zone tumors was constructed and evaluated for gene fusion analysis. TMPRSS2-ERG fusion status was determined using a multicolor interphase fluorescence in situ hybridization assay for ERG break-apart. The median age of the patients was 59 years. Prostatectomy Gleason score was 6 in 21, 7 in 34, and ?8 in 7 cases. Median tumor volume was 200?mm(2). TMPRSS2-ERG gene fusion was present in 7/59 (12%) transition zone, and in 12/35 (34%) peripheral zone tumors. Transition zone fusion-positive cases were larger than their negative counterparts. No significant correlation was found between fusion status and Gleason score or pathologic stage. Gene fusion through deletion occurred in 4/7 transition zone and 7/12 peripheral zone tumors. Transition zone prostate cancers are considered biologically and genetically different from peripheral zone tumors. Although ERG rearrangement is more common in peripheral zone tumors, we have detected TMPRSS2-ERG fusion in a subset of transition zone cancers (12%). The lower frequency of gene fusion in transition zone prostate cancer may suggest distinct molecular alterations from peripheral zone tumors and the association with a high tumor volume may indicate a growth advantage for transition zone tumors harboring the gene fusion. Further studies are necessary to confirm this hypothesis.
Related JoVE Video
Single focus prostate cancer: pathological features and ERG fusion status.
J. Urol.
PUBLISHED: 06-14-2010
Show Abstract
Hide Abstract
We evaluated the clinicopathological characteristics of single focus prostate cancer in radical prostatectomies, its clinical relevance and the occurrence of TMPRSS2-ERG rearrangement.
Related JoVE Video
Clinicopathological features of prostate cancers detected after an initial diagnosis of atypical glands suspicious for cancer.
Pathology
PUBLISHED: 05-05-2010
Show Abstract
Hide Abstract
A diagnosis of atypical glands suspicious for cancer (ATYP) in prostate needle biopsy is associated with approximately a 40-50% risk of detecting prostate cancer in subsequent biopsies. Pathological characteristics of prostate cancer following an initial diagnosis of ATYP are rarely studied.
Related JoVE Video
TMPRSS2-ERG gene fusion prevalence and class are significantly different in prostate cancer of Caucasian, African-American and Japanese patients.
Prostate
PUBLISHED: 04-12-2010
Show Abstract
Hide Abstract
Prostate cancer (PCa) exhibits significant differences in prevalence and mortality among different ethnic groups. The underlying genetics is not well understood. TMPRSS2-ERG fusion is a common recurrent chromosomal aberration in PCa and is however not studied among different ethnic groups. We examined the prevalence and class of TMPRSS2-ERG gene fusion in PCa from Caucasian, African-American, and Japanese patients.
Related JoVE Video
Multifocal high grade prostatic intraepithelial neoplasia is a risk factor for subsequent prostate cancer.
J. Urol.
PUBLISHED: 03-22-2010
Show Abstract
Hide Abstract
The risk of under diagnosed or development of subsequent prostate cancer and the treatment of patients diagnosed with high grade prostatic intraepithelial neoplasia remain controversial. We evaluated the relationship between high grade prostatic intraepithelial neoplasia on initial biopsy and the future presence of prostate cancer.
Related JoVE Video
ETS gene aberrations in atypical cribriform lesions of the prostate: Implications for the distinction between intraductal carcinoma of the prostate and cribriform high-grade prostatic intraepithelial neoplasia.
Am. J. Surg. Pathol.
PUBLISHED: 03-12-2010
Show Abstract
Hide Abstract
Atypical cribriform lesions (ACLs) of the prostate consist of cribriform glands lined with cytologically malignant cells with partial or complete basal cell lining. It may represent cribriform "high-grade prostatic intraepithelial neoplasia" (HGPIN) or "intraductal carcinoma of the prostate" (IDC-P), which is almost always associated with clinically aggressive prostate carcinoma (PCa). Distinction between these 2 lesions has profound clinical significance, especially on needle biopsies. However, there are lesions that do not fully satisfy the criteria for IDC-P yet are worse than typical HGPIN and are difficult to distinguish based on morphologic criteria alone.
Related JoVE Video
Synchronized real-time ultrasonography and three-dimensional computed tomography scan navigation during percutaneous renal cryoablation in a porcine model.
J. Endourol.
PUBLISHED: 03-12-2010
Show Abstract
Hide Abstract
To investigate the accuracy of percutaneous cryoablation for kidney tumors performed under combined real-time ultrasonography (US) and three-dimensional (3D) CT scan navigation in a porcine model.
Related JoVE Video
Can saturation biopsy predict prostate cancer localization in radical prostatectomy specimens: a correlative study and implications for focal therapy.
Urology
PUBLISHED: 03-05-2010
Show Abstract
Hide Abstract
To determine whether saturation needle biopsy of the prostate (SBx) can accurately predict prostate cancer (PCA) location in radical prostatectomy (RP) specimens. The success of focal therapy for PCA relies on accurate mapping of cancer before the procedure.
Related JoVE Video
Atypical cribriform lesions of the prostate: relationship to prostatic carcinoma and implication for diagnosis in prostate biopsies.
Am. J. Surg. Pathol.
PUBLISHED: 02-26-2010
Show Abstract
Hide Abstract
Atypical cribriform lesions of the prostate (ACL) are cribriform glands lined by cytologically malignant cells with partial or complete basal cell lining. They represent cribriform high-grade PIN (cribriform HGPIN), which can be an isolated finding not associated with PCa (isolated ACL), or "intraductal carcinoma (IDC-P)" that is almost always associated with infiltrative high-grade prostate carcinoma (PCa) (cancer-associated ACL, ACL-PCa). We report the incidence, topographic relation to cancer, and morphologic differences of these 2 lesions in radical prostatectomy and discuss the potential biologic basis and implication for diagnosis in prostate biopsy. ACL was defined as cribriform glands comprising cytologically malignant cells that spanned the entire glandular lumens with partial or complete basal cell lining confirmed by basal cell immunostaining. ACL intermixed with, or within 3 mm from the border of infiltrative PCa was categorized as ACL-PCa and was considered to be equivalent to IDC-P. ACLs other than ACL-PCa were considered as isolated ACL and equivalent to cribriform HGPIN. These histologic features of ACL were reviewed: number of ACL/prostate gland, size, glandular contour (round, irregular, branching), architectural pattern (dense cribriform, irregular cribriform, solid), comedonecrosis, and nuclear features (round and uniform, round with varying sizes, pleomorphic, giant nuclei [6x adjacent nuclei]). In 117 consecutive radical prostatectomy specimens, ACL-PCa and isolated ACLs were found in 21 (17.9%) and 15 (12.8%), respectively. ACL-PCa was more common in PCa with Gleason score more than or equal to 7 and higher tumor volume. The isolated ACLs were more common in Gleason score 6 PCa and their incidence was not significantly different among PCa with different tumor volumes. The mean number of ACL per prostate was 23.8 for ACL-PCa and 2.4 for isolated ACL (P=0.008). The size ranged from 0.2 to 9.0 mm for ACL-PCa, and from 0.2 to 1 mm for isolated ACL. The branching contour was present in 36/43 ACL-PCa, but only in 1/23 isolated ACL (P<0.001). The dense cribriform and solid architecture were present in 6 (14.0%) and 4 (9.3%) of ACL-PCa, but none of the isolated ACLs. Comedonecrosis was present in 14/43 (32.6%) ACL-PCa, and in none of the isolated ACL (P=0.001). The pleomorphic nuclei or giant nuclei at least 6X of the adjacent nuclei, were present in 12 (27.9%) ACL-PCa, but in none of the isolated ACL (P=0.005). ACL can be found both in association with PCa or without associated infiltrative PCa. Isolated ACL is uncommon, and the overwhelming majority of ACLs is associated with high grade (GS> or =7) and high-volume PCa and represents IDC-P. Large gland size (>1 mm), large focus involving many glands (number>6), complex architecture, and high-grade nuclei are characteristic of IDC-P. However, cribriform HGPIN and IDC-P overlap at the "low grade" architectural and morphologic spectrum and are difficult to distinguish based on morphologic criteria alone. If a biopsy contains a small number of ACL glands with "low grade" morphology, it should be diagnosed as "atypical cribriform lesion, cannot distinguish between cribriform HGPIN and IDC-P" and a repeat biopsy should be strongly recommended to rule out unsampled PCa. In contrast, if a biopsy contains ACL with one or several features of large focus, architectural complexity with large branching glands, pleomorphic or giant nuclei, or comedonecrosis, the biopsy should be diagnosed as IDC-P and definitive therapy should be recommended.
Related JoVE Video
Importance of additional "extreme" anterior apical needle biopsies in the initial detection of prostate cancer.
Urology
PUBLISHED: 01-18-2010
Show Abstract
Hide Abstract
To describe our experience of adding extreme apical cores in men undergoing initial biopsy. Prostate cancer detection efforts have focused on increasing the number of cores. A more significant factor, however, may be their location. Laterally directed and apical cores have been associated with the highest cancer detection rate, especially the apical cores for men undergoing repeated biopsies.
Related JoVE Video
Renal tubulocystic carcinoma is closely related to papillary renal cell carcinoma: implications for pathologic classification.
Am. J. Surg. Pathol.
PUBLISHED: 11-10-2009
Show Abstract
Hide Abstract
Tubulocystic carcinoma of the kidney (TC-RCC) is a rare renal tumor with unique gross and microscopic features unlike other types of renal cell carcinoma (RCC). Several recent studies recommend that it should be classified as a distinct RCC subtype. In this study, we provide pathologic and cytogenetic evidence supporting that TC-RCC is closely related to papillary RCC (PRCC). This study included 20 cases of renal tumors that partially or exclusively comprised a TC-RCC component. Pathologic examination documented the gross and microscopic features of TC-RCC, including multicentricity and the presence of concomitant PRCC and papillary adenoma. Formalin-fixed, paraffin-embedded sections from 12 TC-RCC and 20 PRCC were subjected to a multicolor fluorescence in situ hybridization assay containing probes for chromosomes 7, 17, and Y. One hundred nuclei were examined to enumerate the copy numbers of chromosomes in each tumor and its corresponding normal kidney tissue. A tumor with a percentage of cells harboring a chromosomal change > or = mean+3 SD of normal tissue was considered to harbor that chromosomal change, and a tumor with a percentage of cells with null Y chromosome count (loss of Y chromosome) > or = mean+3 SD of normal tissue was considered to harbor Y chromosome loss. Four of the 20 TC-RCCs were multicentric. Ten had associated PRCC or papillary adenoma within the same kidney as the TC-RCC. In 4 cases, the tubulocystic and papillary components were admixed together within the same lesion. The tumor cells lining both the tubulocystic and papillary components had similar cytologic features. Ten of 12 TC-RCCs had a chromosome 7 gain, 8 of 12 cases had a chromosome 17 gain, and 8 of 9 cases had a loss of Y chromosome. Six of 9 cases with all 3 chromosomes studied had a gain of chromosomes 7 and 17 and a loss of Y chromosome. Our study shows that TC-RCCs and PRCCs are closely related entities. With its distinctive gross and microscopic features, TC-RCC may be considered a unique "morphologic entity." However, before it is accepted as a distinct renal cell carcinoma subtype, further studies are needed to document a characteristic molecular signature associated with this tumor.
Related JoVE Video
Ductal adenocarcinoma of the prostate diagnosed on transurethral biopsy or resection is not always indicative of aggressive disease: implications for clinical management.
BJU Int.
PUBLISHED: 08-25-2009
Show Abstract
Hide Abstract
To report the clinicopathological characteristics of 23 cases of ductal adenocarcinoma of the prostate (DCP) and discuss the implications for clinical management, as DCP is considered an aggressive subtype of prostate adenocarcinoma (PA).
Related JoVE Video
The Epstein criteria predict for organ-confined but not insignificant disease and a high likelihood of cure at radical prostatectomy.
Eur. Urol.
PUBLISHED: 07-27-2009
Show Abstract
Hide Abstract
Few reports attempt to validate the role of Epstein criteria in selecting patients for an active surveillance protocol.
Related JoVE Video
Are prostate needle biopsies predictive of the laterality of significant cancer and positive surgical margins?
BJU Int.
PUBLISHED: 07-02-2009
Show Abstract
Hide Abstract
To determine whether data obtained from preoperative prostate needle biopsy can predict the laterality of significant cancer and positive surgical margins on final-specimen pathology after laparoscopic radical prostatectomy (LRP).
Related JoVE Video
Microscopic bladder neck involvement by prostate carcinoma in radical prostatectomy specimens is not a significant independent prognostic factor.
Mod. Pathol.
PUBLISHED: 05-27-2009
Show Abstract
Hide Abstract
The independent prognostic importance of microscopic bladder neck involvement by prostate cancer in radical prostatectomy is questionable. We studied a cohort of 1845 patients to determine the significance of microscopic bladder neck involvement. Bladder neck involvement was defined as prostate cancer present within the coned bladder neck. We further categorized the cases as true bladder neck involvement and false bladder neck involvement. True bladder neck involvement required prostate cancer within thick smooth muscle bundles without intermixed benign prostatic glands. False bladder neck involvement was characterized by prostate cancer intermixed with benign prostatic glands. Bladder neck involvement was analyzed in relation to preoperative serum prostate-specific antigen (PSA) level, extraprostatic extension, seminal vesicle involvement, positive surgical margin, lymph node involvement, radical prostatectomy Gleason score, and tumor volume. Of the 90 patients (4.9%) with microscopic bladder neck involvement, 63 were further classified as true bladder neck involvement and 27 as false bladder neck involvement. In univariate model, both types of bladder neck involvement (P<0.001), true (P<0.001), and false (P=0.040), were significantly associated with increased PSA-recurrence risk compared to bladder neck negative cases. In multivariate model the PSA-recurrence relative risk associated with bladder neck involvement (true or false) was not a significant independent prognostic factor. Extraprostatic extension, seminal vesicle involvement, positive surgical margin, lymph node involvement, PSA, and Gleason score were significant independent predictors of PSA recurrence. The time to biochemical recurrence in patients with bladder neck involvement was similar to that of pT2 with positive surgical margin or pT3a with negative surgical margin patients (Kaplan-Meier curves). Bladder neck involvement was associated with other adverse pathologic features, but was not an independent predictor of PSA recurrence. In view of the previous and current data, the staging system for bladder neck involvement should be revised and patients may be best categorized as having pT3a disease.
Related JoVE Video
KTP laser nerve sparing radical prostatectomy: comparison of ultrasonic and cold scissor dissection on cavernous nerve function.
J. Urol.
PUBLISHED: 04-17-2009
Show Abstract
Hide Abstract
Energy sources used during nerve sparing radical prostatectomy are known to compromise cavernous nerve function. Lasers offer the potential for accurate dissection while minimizing collateral injury to delicate neural structures. We evaluated cavernous nerve function following KTP laser dissection and compared outcomes to those of ultrasonic shears and cold scissor dissection.
Related JoVE Video
Renal angiomyolipoma: clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association.
Am. J. Surg. Pathol.
PUBLISHED: 02-20-2009
Show Abstract
Hide Abstract
The majority of renal angiomyolipoma (AML) is sporadic and occasionally it occurs as part of tuberous sclerosis complex (TSC). Epithelioid AML (EAML), an uncommon variant, is considered potentially malignant based on anecdotal case reports. The prognostic significance of epithelioid component in an otherwise typical AML is uncertain. We studied 194 AMLs for the clinicopathologic features of epithelioid and TSC-associated AMLs. Epithelioid component was present in 15 cases (7.7%) with an average amount of 51% (range: 10% to 100%). Histologically, the epithelioid tumor cells were categorized into small, intermediate, and large cell type based on the cell size. Worrisome histologic features were seen in many EAMLs, including coagulative tumor necrosis in 27% (4/15), nuclear atypia in 93% (14/15), mitosis in 47% (7/15), and atypical mitosis in 1 case. All 15 EAML patients had a mean follow-up time of 5.1 years and none had local recurrence or distant metastasis. Sixteen (8.2%) AMLs occurred in patients with definitive TSC. Three histologic features, namely microscopic AML foci, epithelioid component, and epithelial cysts, were present in 10 (62.5%), 4 (25%), and 44% (7/16), respectively, of TSC-associated AMLs, compared with 11 (6.2%), 11 (6.2%), and 6 (3.4%), respectively, in non-TSC-associated AMLs (P value all <0.01). In summary, all 15 cases of EAMLs in our study had benign clinical outcomes despite adverse pathologic features. Epithelioid component, epithelial cysts, and microscopic AML foci are strongly associated with TSC and the presence of all 3 features should raise strong suspicion for TSC.
Related JoVE Video
Adult cystic nephroma and mixed epithelial and stromal tumor of the kidney are the same disease entity: molecular and histologic evidence.
Am. J. Surg. Pathol.
PUBLISHED: 02-04-2009
Show Abstract
Hide Abstract
Adult cystic nephroma (CN) and mixed epithelial and stromal tumor of the kidney (MEST) are considered as separate entities in the 2004 World Health Organization classification of renal neoplasms. Recent studies suggested that the two share clinicopathologic features and may represent the same disease process of varying morphology. However, definitive genetic evidence is lacking. We examined their relationship using gene expression profiling and histologic analysis. Gene expression profiles of 3 CN and 3 MEST were analyzed using HGU133 Plus 2.0 microarrays (Affymetrix) and were compared with each other and also with 48 other renal tumors and 13 normal kidneys. Histologic examination of 26 CN and 13 MEST focused on the cystic septal thickness, cyst-to-stroma ratio, stromal cellularity and composition, types of epithelial cells lining cysts and glands, and estrogen and progesterone receptors expression. Patients age, sex distribution, and tumor size were similar between the two. They also shared many histologic features, including lining epithelium of cysts and glands, stromal cellularity and composition. Unsupervised clustering of mRNA expression profiles demonstrated that they had very similar expression profiles that were distinct from other renal tumors. By microarray analysis, progesterone receptor expression was significantly higher in CN and MEST relative to both normal and other renal tumors, while estrogen receptor expression was not. By immunohistochemistry, expression of both receptors was similar between CN and MEST. This study provides the most convincing molecular evidence that CN and MEST represent different parts of the morphologic spectrum of the same disease.
Related JoVE Video
EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent.
Science
Show Abstract
Hide Abstract
Epigenetic regulators represent a promising new class of therapeutic targets for cancer. Enhancer of zeste homolog 2 (EZH2), a subunit of Polycomb repressive complex 2 (PRC2), silences gene expression via its histone methyltransferase activity. We found that the oncogenic function of EZH2 in cells of castration-resistant prostate cancer is independent of its role as a transcriptional repressor. Instead, it involves the ability of EZH2 to act as a coactivator for critical transcription factors including the androgen receptor. This functional switch is dependent on phosphorylation of EZH2 and requires an intact methyltransferase domain. Hence, targeting the non-PRC2 function of EZH2 may have therapeutic efficacy for treating metastatic, hormone-refractory prostate cancer.
Related JoVE Video
Dysregulation of cholesterol homeostasis in human prostate cancer through loss of ABCA1.
Cancer Res.
Show Abstract
Hide Abstract
Recent epidemiologic data show that low serum cholesterol level as well as statin use is associated with a decreased risk of developing aggressive or advanced prostate cancer, suggesting a role for cholesterol in aggressive prostate cancer development. Intracellular cholesterol promotes prostate cancer progression as a substrate for de novo androgen synthesis and through regulation of AKT signaling. By conducting next-generation sequencing-based DNA methylome analysis, we have discovered marked hypermethylation at the promoter of the major cellular cholesterol efflux transporter, ABCA1, in LNCaP prostate cancer cells. ABCA1 promoter hypermethylation renders the promoter unresponsive to transactivation and leads to elevated cholesterol levels in LNCaP. ABCA1 promoter hypermethylation is enriched in intermediate- to high-grade prostate cancers and not detectable in benign prostate. Remarkably, ABCA1 downregulation is evident in all prostate cancers examined, and expression levels are inversely correlated with Gleason grade. Our results suggest that cancer-specific ABCA1 hypermethylation and loss of protein expression direct high intracellular cholesterol levels and hence contribute to an environment conducive to tumor progression.
Related JoVE Video
ERG protein expression in human tumors detected with a rabbit monoclonal antibody.
Am. J. Clin. Pathol.
Show Abstract
Hide Abstract
Avian v-ets erythroblastosis virus E26 oncogene homolog (ERG) is highly sensitive and specific for endothelial neoplasms and specific for prostate carcinoma. We characterized a rabbit anti-ERG antibody as an immunohistochemical agent to detect ERG expression in various tumors using tissue microarrays with a wide array of epithelial and mesenchymal tumors. ERG was positive in 63 (38%) of 168 prostate carcinomas and negative in all other epithelial tumors. ERG was positive in all 125 vascular lesions. It was also positive in the sarcomatoid component of a high-grade urothelial carcinoma and 6 (40%) of 15 meningiomas. Twelve (80%) of 15 meningiomas were positive for Fli1, including all 6 ERG-positive cases. Positive immunostaining with this antibody is therefore highly specific for prostate carcinoma and vascular lesions, with a few caveats. ERG is rarely detected in nonvascular mesenchymal tumors with this antibody. Furthermore, about 40% of meningiomas are also positive for ERG immunohistochemically, probably because of cross-reactivity with Fli1.
Related JoVE Video
Expression of ERG protein, a prostate cancer specific marker, in high grade prostatic intraepithelial neoplasia (HGPIN): lack of utility to stratify cancer risks associated with HGPIN.
BJU Int.
Show Abstract
Hide Abstract
Whats known on the subject? and What does the study add? High grade prostatic intraepithelial neoplasia is a pre-malignant lesion to prostate cancer and is associated with 20%-25% risk of prostate cancer in subsequent repeat biopsies. ERG is a highly prostate-cancer-specific marker. Expression of ERG is rare in isolated high grade prostatic intraepithelial neoplasia diagnosed in prostate biopsy and is not associated with cancer risk in subsequent repeat biopsies.
Related JoVE Video
Intraductal carcinoma of the prostate: precursor or aggressive phenotype of prostate cancer?
Prostate
Show Abstract
Hide Abstract
Although the term "intraductal carcinoma of the prostate" (IDC-P) was introduced almost 40 years ago, there is still the lack of appreciation that this entity represents a clinically aggressive disease that continues to be misreported under the diagnostic category of high grade prostatic intraepithelial neoplasia (HGPIN).
Related JoVE Video
High-grade prostatic intraepithelial neoplasia.
Korean J Urol
Show Abstract
Hide Abstract
High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer.
Related JoVE Video
Intraductal carcinoma of the prostate.
Arch. Pathol. Lab. Med.
Show Abstract
Hide Abstract
Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathologic entity, characterized by an expansile proliferation of secretory cells within prostatic ducts and acini that demonstrate marked architectural and cytologic atypia. Intraductal carcinoma of the prostate is strongly associated with high-grade and high-volume, invasive prostate cancer and a poorer prognosis than cases without IDC-P.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.