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Immunohistochemistry using the BRAF V600E mutation‐specific monoclonal antibody VE 1 is not a useful surrogate for genotyping in colorectal adenocarcinoma
Author(s) -
Adackapara Cheryl A,
Sholl Lynette M,
Barletta Justine A,
Hornick Jason L
Publication year - 2013
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12154
Subject(s) - immunohistochemistry , monoclonal antibody , genotyping , adenocarcinoma , mutation , epitope , monoclonal , cancer research , antibody , microbiology and biotechnology , medicine , pathology , biology , immunology , genotype , cancer , genetics , gene
Aims The presence of a BRAF mutation is a strong marker for poor prognosis of colorectal carcinoma ( CRC ), and can be used as evidence of a sporadic mechanism of mismatch repair deficiency. BRAF mutation may also predict resistance to EGFR ‐targeted therapy. A BRAF V600E‐specific antibody has recently become commercially available. The aim of this study was to determine whether immunohistochemistry can predict BRAF mutations in CRC . Methods and results Immunohistochemistry was performed on 52 genotyped CRC cases (17 BRAF mutant, 18 KRAS mutant, 17 BRAF / KRAS wild‐type) with monoclonal antibody VE 1. Cytoplasmic staining was observed in 71% of BRAF V600E mutant tumours (moderate or strong staining in 50% of these cases). Weak cytoplasmic staining was observed in 17% of KRAS mutant tumours and 35% of wild‐type tumours. Non‐specific nuclear staining was common. The sensitivity and specificity of immunohistochemistry with VE 1 for BRAF mutation were 71% and 74%, respectively; when only moderate or strong staining was considered to be positive, the specificity was 100%, but the sensitivity only 35%. Conclusions Immunohistochemistry with VE 1 is not a useful surrogate for genotyping in CRC . Although moderate or strong cytoplasmic staining is specific for BRAF V600E mutations, this antibody is insufficiently sensitive to serve as an effective screening tool.