title: Immunohistochemistry using the BRAF V600E mutation-specific monoclonal antibody VE1 is not a useful surrogate for genotyping in colorectal adenocarcinoma.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  Immunohistochemistry was performed on 52 genotyped CRC cases (17 BRAF mutant, 18 KRAS mutant, 17 BRAF/KRAS wild-type) with monoclonal antibody VE1. 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 VE1 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 VE1 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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Adackapara
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Sholl
authors.forename: Justine A
authors.initials: JA
authors.lastname: Barletta
authors.forename: Jason L
authors.initials: JL
authors.lastname: Hornick
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D050505:Mutant Proteins; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: BRAF; KRAS; colon cancer; predictive markers; targeted therapy