ArticleThe American journal of surgical pathology2014
Detection of the BRAF V600E mutation in colon carcinoma: critical evaluation of the imunohistochemical approach.
Article in The American journal of surgical pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Diagnostic Accuracy of BRAF Immunohistochemistry in Colorectal Cancer: a Meta-Analysis and Diagnostic Test Accuracy Review.Pathology oncology research : POR · 2016Pooled it
- Proficiency test of BRAF immunohistochemistry as a surrogate marker of p.V600E mutation: Assessment of staining and interpretation quality in Taiwan.Virchows Archiv : an international journal of pathology · 2026Article
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- Usefulness of BRAF VE1 immunohistochemistry in non-small cell lung cancers: a multi-institutional study by 15 pathologists in Korea.Journal of pathology and translational medicine · 2022Article
- Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process.Frontiers in chemistry · 2022Article
- BRAF V600E mutation-specific immunohistochemical analysis in ameloblastomas: a 44-patient cohort study from a single institution.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2021Article
- Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors.Cancers · 2021Review
- Preliminary Study on the Identification of BRAFOncoTargets and therapy · 2020Article
- Primary malignant melanoma of esophagus: clinicopathologic characterization of 20 cases including molecular genetic profiling of 15 tumors.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Article
- Immunohistochemistry with Anti-BRAF V600E (VE1) Mouse Monoclonal Antibody is a Sensitive Method for Detection of the BRAF V600E Mutation in Colon Cancer: Evaluation of 120 Cases with and without KRAS Mutation and Literature Review.Pathology oncology research : POR · 2019Review
- SP174 Antibody Lacks Specificity for NRAS Q61R and Cross-Reacts With HRAS and KRAS Q61R Mutant Proteins in Malignant Melanoma.Applied immunohistochemistry & molecular morphology : AIMM · 2018Article
- Histopathological and genotypic characterization of metastatic colorectal carcinoma with PD-L1 (CD274)-expression: Possible roles of tumour micro environmental factors for CD274 expression.The journal of pathology. Clinical research · 2017Article
- Immunohistochemistry cannot replace DNA analysis for evaluation ofOncotarget · 2017Article
- Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation.Oncotarget · 2017Article
- Article
- SP174, NRAS Q61R Mutant-Specific Antibody, Cross-Reacts With KRAS Q61R Mutant Protein in Colorectal Carcinoma.Archives of pathology & laboratory medicine · 2017Article
- Clinicopathologic profile, immunophenotype, and genotype of CD274 (PD-L1)-positive colorectal carcinomas.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2017Article
- Tumor testing to identify lynch syndrome in two Australian colorectal cancer cohorts.Journal of gastroenterology and hepatology · 2017Article
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- Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Recently BRAF V600E mutant-specific antibody (clone VE1) became available to immunohistochemically pinpoint the occurrence of these BRAF-mutant proteins in different tumors, such as colon carcinoma. Detection of BRAF mutations is important for the accurate application of targeted therapy against BRAF serine-threonine kinase activation. In this study, we evaluated 113 colon carcinomas including 95 primary and 27 metastatic tumors with the VE1 antibody using Leica Bond-Max automated immunohistochemistry. To ensure comprehensive BRAF V600E mutation detection, all cases were evaluated using 4 molecular methods (Sanger sequencing, the Cobas 4800 BRAF V600 Mutation Test, BRAF V600 allele-specific polymerase chain reaction, and BRAF V600 quantitative polymerase chain reaction) with nearly 100% concordance. Molecular and immunohistochemical studies were blinded. Furthermore, all cases were evaluated for KRAS and NRAS mutations as parameters mutually exclusive with BRAF mutations offering parallel evidence for BRAF mutation status. Strong to moderate VE1 positivity was seen in 34 tumors. Twelve colon carcinomas showed weak VE1 immunohistochemical staining, and 67 were entirely negative. An identical c.1799T>A single nucleotide substitution leading to the BRAF V600E mutation was identified in 27 of 113 (24%) colon carcinomas. A majority of BRAF-mutant tumors were located in the right side of the colon and had mismatch-repair deficiency. V600E mutation-negative carcinomas were more often sigmoid tumors and usually showed intact mismatch-repair proteins and KRAS or NRAS mutations. The sensitivity and specificity of positive results (strong to moderate staining) of VE1 immunohistochemistry were 85% and 68%, respectively. If any positivity would be considered, then the specificity declined to 51% with no significant improvement of sensitivity. Therefore, only strong positivity should be considered when using the VE1 antibody and Leica Bond-Max automated immunohistochemistry with these parameters. Although VE1 antibody can be useful in the screening of colon carcinomas for BRAF V600E-mutant proteins, molecular genetic confirmation is always necessary for mutation diagnosis.
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