Immunohistochemical detection of the BRAF V600E mutant protein in colorectal cancers in Taiwan is highly concordant with the molecular test

• Published in: Histopathology 2016-07, Vol.69 (1), p.54-62
• Main Authors: Hang, Jen-Fan, Li, Anna Fen-Yau, Chang, Shih-Ching, Liang, Wen-Yih
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Antibodies, Monoclonal; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; BRAF mutation; Cohort Studies; Colon - pathology; colorectal cancer; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Colorectal Neoplasms, Hereditary Nonpolyposis - metabolism; Female; Humans; Lynch syndrome; Male; Middle Aged; Mutant Proteins - genetics; Mutant Proteins - metabolism; Mutation; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins B-raf - metabolism; Rectum - pathology; Sensitivity and Specificity; Sequence Analysis, DNA; Taiwan; VE1 antibody; Young Adult
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.12903

Aims The aims of this study were to investigate the incidence of BRAF mutations in colorectal cancers (CRCs) in Taiwan and the sensitivity and specificity of VE1 immunohistochemistry in detecting the BRAFV600E mutation. Methods and results A total of 425 resected colorectal adenocarcinoma specimens were recruited into this study. Direct Sanger sequencing of exon 15 of the BRAF gene was performed for all cases. The incidence of BRAF mutation was 5.4% (23 of 425). Tissue microarrays were constructed for VE1 immunohistochemistry, and the staining intensity was scored as negative (0), weak (1+), moderate (2+) and strong (3+). In BRAF‐mutated cases, two (8.7%) scored as 0, three (13.0%) as 1+, 13 (56.5%) as 2+ and five (21.7%) as 3+. Among 402 BRAF wild‐type cases, five (1.2%) were scored as 1+, while the others were negative. The sensitivity and specificity of VE1 expression in detecting the BRAF mutation was 91.3% and 98.8%, respectively. Conclusions Immunohistochemistry for VE1 antibody is a sensitive and specific marker for detection of BRAF mutations in CRCs. Incorporation of VE1 immunohistochemistry into Lynch syndrome screening protocol may be a reliable and cost‐effective method.