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Find video protocols related to scientific articles indexed in Pubmed.
Automated processing of fluorescence in-situ hybridization slides for HER2 testing in breast and gastro-esophageal carcinomas.
Exp. Mol. Pathol.
PUBLISHED: 06-09-2014
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HER2 fluorescence in-situ hybridization (FISH) is used in breast and gastro-esophageal carcinoma for determining HER2 gene amplification and patients' eligibility for HER2 targeted therapeutics. Traditional manual processing of the FISH slides is labor intensive because of multiple steps that require hands on manipulation of the slides and specifically timed intervals between steps. This highly manual processing also introduces inter-run and inter-operator variability that may affect the quality of the FISH result. Therefore, we sought to incorporate an automated processing instrument into our FISH workflow.
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Molecular testing for the BRCA1 and BRCA2 Ashkenazi Jewish founder mutations: a report on the College of American Pathologists proficiency testing surveys.
Genet. Med.
PUBLISHED: 03-11-2014
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Purpose:The purpose of this study was to analyze laboratory performance on proficiency testing surveys offered jointly by the College of American Pathologists/American College of Medical Genetics and Genomics biannually for the three common Ashkenazi Jewish founder mutations in the BRCA1 and BRCA2 genes.Methods:Survey responses were analyzed for accuracy of genotype determination and the associated clinical interpretation. Data on an individual laboratory's participation over time, number of samples tested, turnaround time, and test methodology were also reviewed.Results:Between 2003 and 2012, 23 US laboratories and 39 international laboratories participated. There were six genotyping errors, with a corresponding analytical sensitivity of 99.0% (479/484 challenges; 95% confidence interval: 97.6-99.7%) and an analytic specificity of 99.9% (870/871; 95% confidence interval: 99.4-99.9%). Among the 1,325 clinical interpretations, 92.5% (1,226/1,325; 95% confidence interval: 91.0-93.9%) matched the intended response. Most of the 99 discrepancies-81% (80/99)-incorrectly interpreted the risk for a negative test result as having a lifetime risk of breast cancer "that is the same as that in the general population" instead of "that cannot be determined without BRCA mutation testing of the affected relative." Conclusion:Clinical laboratories demonstrated excellent analytical sensitivity and specificity. The clinical interpretation requires additional education, focusing on the clinical interpretation of negative test results for these three mutations.Genet Med advance online publication 19 June 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.77.
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Lynch syndrome presenting as endometrial cancer.
Clin. Chem.
PUBLISHED: 11-05-2013
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Lynch syndrome (LS) is the most common form of the hereditary colon cancer syndromes. Because of its high prevalence, a nationwide campaign has begun to screen all colorectal cancers for the genetic abnormalities associated with LS.
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A comprehensive assay for CFTR mutational analysis using next-generation sequencing.
Clin. Chem.
PUBLISHED: 06-17-2013
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Cystic fibrosis is a life-threatening genetic disorder that has been associated with mutations in the CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] gene. Hundreds of CFTR mutations have been detected to date. Current CFTR genotyping assays target a subset of these mutations, particularly a mutation panel recommended by the American College of Medical Genetics for carrier screening of the general population. Fast sequencing of the entire coding sequence in a scalable manner could expand the detection of CFTR mutations and facilitate management of costs and turnaround times in the clinical laboratory.
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Validation of a solid-phase electrochemical array for genotyping hepatitis C virus.
Exp. Mol. Pathol.
PUBLISHED: 03-15-2013
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Hepatitis C viral infection is a major cause of progressive liver disease. HCV genotype is one of the most significant baseline predictors of response to HCV antiviral therapy. The objective was to evaluate an HCV genotyping method that targets the 5-untranslated region (UTR) to detect genotypes/subtypes using the GenMark eSensor® XT-8 system. The HCV amplicon of major genotypes/subtypes from the Roche TaqMan® HCV assay served as a template for the nested PCR followed by a direct analysis on the XT-8 detection system. The assay was validated for limit of detection (LOD), specificity, accuracy and precision. The LOD determined was below 175 IU/ml for all the subtypes except 6ab. The genotypes detected using this assay were in concordance with the LiPA assay. The high performance characteristics (LOD, specificity, intra- and inter-assay precision, and accuracy), make this assay particularly well suited for clinical HCV genotyping in order to guide antiviral therapy.
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ZEB1 overexpression associated with E-cadherin and microRNA-200 downregulation is characteristic of undifferentiated endometrial carcinoma.
Mod. Pathol.
PUBLISHED: 01-25-2013
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Undifferentiated endometrial carcinomas are very aggressive high-grade endometrial carcinomas that are frequently under-recognized. This study aimed to analyze the molecular alterations underlying the development of these endometrial carcinomas, focusing on those related to dedifferentiation. We assessed a series of 120 tumors: 57 grade 1 and 2 endometrioid endometrial carcinomas, 15 grade 3 endometrioid endometrial carcinomas, 27 endometrial serous carcinomas, and 21 undifferentiated endometrial carcinomas. We found a high frequency of DNA mismatch repair deficiency (38%) and moderate rate of p53 overexpression (?33%) in undifferentiated carcinomas. In contrast to the characteristic endometrioid phenotype, there was a dramatic downregulation of E-cadherin expression in the undifferentiated subtype. Quantitative methylation studies dismissed CDH1 promoter hypermethylation as the mechanism responsible for this change in gene expression, while immunohistochemistry revealed that the E-cadherin repressor ZEB1 was frequently overexpressed (62%) in undifferentiated endometrial carcinomas. This finding was accompanied by a sharp downregulation in the expression of the miR-200 family of microRNAs, well-known targets of ZEB1. Furthermore, there was enhanced expression of epithelial-to-mesenchymal transition markers in undifferentiated endometrial carcinomas, such as N-cadherin, cytoplasmic p120, and osteonectin. In addition, HMGA2, a regulator of epithelial-to-mesenchymal transition that is expressed in aggressive endometrial tumors, such as endometrial serous carcinomas and carcinosarcomas, was expressed in >20% of undifferentiated carcinomas. These results suggest that ZEB1 overexpression, associated with E-cadherin and miR-200s downregulation, and the expression of mesenchymal markers might enhance the metastatic potential of undifferentiated endometrial carcinomas, leading to a poor prognosis. In addition, our observations suggest that the immnohistochemical analysis of E-cadherin and ZEB1 can aid in the differential diagnosis of the more agressive undifferentiated endometrial carcinomas from grade 3 endometrioid carcinomas.
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Human epidermal growth factor receptor 2 testing in gastroesophageal cancer: correlation between immunohistochemistry and fluorescence in situ hybridization.
Arch. Pathol. Lab. Med.
PUBLISHED: 10-29-2011
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Patients with advanced gastroesophageal cancer have poor survival with current therapy. Human epidermal growth factor receptor 2 (HER2) represents a promising therapeutic target, but the optimal HER2 testing strategy is not yet defined.
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BRAF mutation analysis of fine-needle aspiration biopsies of papillary thyroid carcinoma: impact on diagnosis and prognosis.
Acta Cytol.
PUBLISHED: 07-04-2011
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The BRAF V600E mutation has been associated with aggressive disease in papillary thyroid carcinoma (PTC). Molecular testing has been proposed as a useful adjunct to cytology in the diagnosis of malignancy and for tailoring clinical management. The aims of our study were to evaluate the BRAF mutational status using archived fine-needle aspiration biopsy (FNAB) material from patients with long-term follow-up and to correlate it with the original cytology diagnosis, clinicopathological stage at surgery, and prognosis.
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The human epidermal growth factor receptor 2 (HER2).
Clin. Chem. Lab. Med.
PUBLISHED: 06-08-2011
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The declared "war on cancer" aimed to eradicate this disease using our knowledge of cancer cell biology to develop novel therapeutics. One such target of these novel therapies has been the human epidermal growth factor receptor 2 (HER2) gene. Unique in the approach to abolishing function of this gene coded receptor, it was the first target of new monoclonal antibody therapy targeting the extracellular receptor and now also a target of small molecule drugs against the intracellular tyrosine kinase domain. In this instance, it was also one of the first applications of personalized medicine requiring companion diagnostics. In this manuscript, we review the biology and clinical applications of HER2 as a biomarker of disease and as a therapeutic target.
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Predicting biochemical recurrence-free survival for patients with positive pelvic lymph nodes at radical prostatectomy.
J. Urol.
PUBLISHED: 05-15-2010
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We evaluated predictors of freedom from biochemical recurrence in patients with pelvic lymph node metastasis at radical prostatectomy.
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Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms.
Mod. Pathol.
PUBLISHED: 03-19-2010
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Carcinomas of the endometrium and ovary with undifferentiated components are uncommon neoplasms that are likely underdiagnosed. They are important to recognize as they have been shown to be clinically aggressive. We identified 32 carcinomas with undifferentiated components as defined by Silva and co-workers, 26 endometrial and 6 of ovarian origin. The patient age ranged from 21 to 76 years (median 55); 40% of patients were
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A validation study of a new molecular diagnostic assay: the Dartmouth-Hitchcock Medical Center experience with the GeneSearch BLN assay in breast sentinel lymph nodes.
Exp. Mol. Pathol.
PUBLISHED: 10-09-2009
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Sentinel lymph node (SLN) processing remains variable in terms of performing multiple tissue levels and immunohistochemical (IHC) or PCR-based assays. A rapid and reliable molecular pathology assay, as an adjunct to routine SLN processing, could minimize and standardize the histologic evaluation needed for an accurate and clinically significant diagnosis. We compared the recently FDA-approved Veridex GeneSearch Breast Lymph Node (BLN) Assay (Veridex, LLC; Warren, NJ), a real time reverse transcriptase-polymerase chain reaction assay that is designed to detect metastases >0.2 mm, with our standard lymph node processing.
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Fatal aortic dissection due to a fulminant variety of isolated aortitis.
J Clin Rheumatol
PUBLISHED: 09-08-2009
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Aortitis is typically a chronic, progressive disease manifestation associated with large vessel vasculitidies, most notably giant cell, Takayasu arteritis, and a newly described entity, isolated aortitis. The aortitis may lead to aneurysm formation and symptoms associated with branch vessel occlusion in these diseases, but aortic dissection is rare and usually a late complication of smoldering, incompletely treated disease. We present a case of aortitis in a previously healthy 39-year-old man who succumbed to aortic dissection hours after the onset of symptoms. No aneurysm or fibrosis was found on postmortem examination. The inflammation was characterized by disruption of the media with patchy transmural chronic and focally acute inflammatory infiltrate. We review case reports of other individuals with aortitis, who initially or very early in their course presented with aortic dissection in the absence of known rheumatic disease and most without evidence of aneurysm formation. We believe that this represents a process characterized by an aggressive vasculitis of the aorta with its own clinical features, a fulminant variety of isolated aortitis.
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Distinct profile of driver mutations and clinical features in immunomarker-defined subsets of pulmonary large-cell carcinoma.
Mod. Pathol.
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Pulmonary large-cell carcinoma-a diagnostically and clinically controversial entity-is defined as a non-small-cell carcinoma lacking morphologic differentiation of either adenocarcinoma or squamous cell carcinoma, but suspected to represent an end stage of poor differentiation of these tumor types. Given the recent advances in immunohistochemistry to distinguish adenocarcinoma and squamous cell carcinoma, and the recent insights that several therapeutically relevant genetic alterations are distributed differentially in these tumors, we hypothesized that immunophenotyping may stratify large-cell carcinomas into subsets with distinct profiles of targetable driver mutations. We therefore analyzed 102 large-cell carcinomas by immunohistochemistry for TTF-1 and ?Np63/p40 as classifiers for adenocarcinoma and squamous cell carcinoma, respectively, and correlated the resulting subtypes with nine therapeutically relevant genetic alterations characteristic of adenocarcinoma (EGFR, KRAS, BRAF, MAP2K1/MEK1, NRAS, ERBB2/HER2 mutations and ALK rearrangements) or more common in squamous cell carcinoma (PIK3CA and AKT1 mutations). The immunomarkers classified large-cell carcinomas as variants of adenocarcinoma (n=62; 60%), squamous cell carcinoma (n=20; 20%) or marker-null (n=20; 20%). Genetic alterations were found in 38 cases (37%), including EGFR (n=1), KRAS (n=30), BRAF (n=2), MAP2K1 (n=1), ALK (n=3) and PIK3CA (n=1). All molecular alterations characteristic of adenocarcinoma occurred in tumors with immunoprofiles of adenocarcinoma or marker-null, but not in tumors with squamous immunoprofiles (combined mutation rate 50% vs 30% vs 0%, respectively; P<0.001), whereas the sole PIK3CA mutation occurred in a tumor with squamous profile (5%). Furthermore, marker-null large-cell carcinomas were associated with significantly inferior disease-free (P<0.001) and overall (P=0.001) survival. In conclusion, the majority (80%) of large-cell carcinomas can be classified by immunomarkers as variants of adenocarcinoma or squamous cell carcinoma, which stratifies these tumors into subsets with a distinct distribution of driver mutations and distinct prognoses. These findings have practical implications for diagnosis, predictive molecular testing and therapy selection.
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Pathological features of lymph node metastasis for predicting biochemical recurrence after radical prostatectomy for prostate cancer.
J. Urol.
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Subclassification of nodal stage may have prognostic value in men with lymph node metastasis at radical prostatectomy. We explored the role of extranodal extension, size of the largest metastatic lymph node and the largest metastasis, and lymph node density as predictors of biochemical recurrence.
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Automation of genomic DNA isolation from formalin-fixed, paraffin-embedded tissues.
Pathol. Res. Pract.
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Isolation of DNA from formalin-fixed, paraffin-embedded (FFPE) tissue remains a laborious task for clinical laboratories and researchers who need to screen several samples for genetic variants. The objective of this study was to evaluate DNA isolation methods from FFPE tissues and to choose an efficient method with less hands-on time to obtain DNA of optimum concentration and purity for use in routine molecular diagnostic assays. Three methods were compared in this study: Gentra Puregene Tissue Kit, EZ1 DNA Tissue Kit and QIAamp FFPE Tissue Kit. Samples consisted of FFPE tissues of head/neck and lung tumor resections. Quality control for the extraction process end product included determination of the concentration and purity of isolated DNA and the ability to amplify a housekeeping gene, GAPDH, using real-time PCR assay. The hands-on-time required was less for the EZ1 protocol compared to the other methods. The average DNA concentration obtained was 112, 61 and 40 ng/?l, respectively, for the Gentra Puregene Tissue Kit, Qiagen EZ1 DNA Tissue Kit and QIAamp FFPE Tissue Kit. The purity and quality of samples obtained using the different DNA isolation methods were comparable. Comparative evaluation of three DNA isolation methods indicated that the Qiagen EZ1 method surpassed the other methods with reduced hands-on-time to produce optimum concentration of quality DNA for use in routine molecular analyses.
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Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations.
Clin. Cancer Res.
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There is persistent controversy as to whether EGFR and KRAS mutations occur in pulmonary squamous cell carcinoma (SQCC). We hypothesized that the reported variability may reflect difficulties in the pathologic distinction of true SQCC from adenosquamous carcinoma (AD-SQC) and poorly differentiated adenocarcinoma due to incomplete sampling or morphologic overlap. The recent development of a robust immunohistochemical approach for distinguishing squamous versus glandular differentiation provides an opportunity to reassess EGFR/KRAS and other targetable kinase mutation frequencies in a pathologically homogeneous series of SQCC.
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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.