BRAF V600E mutation detection by immunohistochemistry in colorectal carcinoma. Issue 8 (7th May 2013)

• Record Type: Journal Article
• Authors: Affolter, Kajsa; Samowitz, Wade; Tripp, Sheryl; Bronner, Mary P.
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 8(2013:Aug.)
• Page Start: 748
• Page End: 752
• Publication Date: 2013-05-07
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22070
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The serine/threonine‐protein kinase B‐raf (<italic>BRAF</italic>) is an oncogene mutated in various neoplasms, including 5–15% of colorectal carcinomas. The T1799A point mutation, responsible for a large majority of these alterations, results in an amino acid substitution (V600E) causing the constitutive activation of a protein kinase cascade. BRAF V600E in <italic>MLH1</italic> deficient tumors implicates somatic tumor‐only methylation of the <italic>MLH1</italic> promoter region instead of a germline <italic>MLH1</italic> mutation. BRAF V600E also predicts poor prognosis in microsatellite stable colorectal cancers and may be a marker of resistance to anti‐EGFR therapy in metastatic disease. Currently, only molecular methods are available for assessing <italic>BRAF</italic> mutational status. An immunohistochemical approach is evaluated here. Colon cancers from 2008 to 2012 tested by pyrosequencing for <italic>BRAF</italic> V600E mutation were selected. A total of 31 tumors with (<italic>n</italic> = 14) and without (<italic>n</italic> = 17) the <italic>BRAF</italic> V600E mutation were analyzed by immunohistochemistry using a commercially available antibody specific to the V600E‐mutated protein. All 14 colorectal carcinomas with the <italic>BRAF</italic> V600E mutation demonstrated cytoplasmic positivity in tumor cells with the anti‐BRAF antibody. In a minority of cases, staining intensity for the mutated tumor samples was weak (<italic>n</italic> = 2) or heterogeneous (<italic>n</italic> = 4); however, the majority of cases showed diffuse, strong cytoplasmic positivity (8 of 14 cases). None of the 17 <italic>BRAF</italic> wild‐type colorectal cancers showed immunoreactivity to the antibody. The overall sensitivity and specificity of the immunohistochemical BRAF V600E assay was 100%. Detection of the <italic>BRAF</italic> V600E mutation in colorectal cancer by immunohistochemistry is a viable alternative to molecular methods. © 2013 Wiley Periodicals, Inc.</p> </abstract>