Journal of pathology and translational medicine 2018 03 29() doi 10.4132/jptm.2018.03.28
BRAF mutation has been recognized as an important biomarker of colorectal cancer (CRC) for targeted therapy and prognosis prediction. However, sequencing of every CRC case is not cost-effective. Since an antibody specific for BRAF V600E mutant protein was introduced, we examined the utility of BRAF VE1 immunohistochemistry for evaluating BRAF mutations in CRC.
Materials and Methods
Fifty-one BRAF-mutated and age, sex-matched 100 BRAF-wild type CRCs were selected at Asan Medical Center from 2005 to 2015. A tissue microarray was constructed and stained with BRAF VE1 antibody.
Forty-nine of the 51 BRAF-mutant CRCs (96.1%) showed more than moderate cytoplasmic staining, except for two weakly stained cases. However, 6 of 100 BRAF-wild type cases were also stained with BRAF VE1 antibody (four weakly stained and two moderately stained cases). In addition, normal colonic crypts showed weak nonspecific stains and some CRC cases exhibited moderate nuclear reactivity (3 BRAF-mutant and 10 BRAF-wild type cases). BRAF-mutated CRC patients had higher pathologic stages and worse survival than BRAF-wild type patients.
BRAF VE1 immunohistochemistry showed high sensitivity and specificity, but occasionally non-specific staining in tumor cell nuclei and normal colonic crypts, which may limit their routine clinical use. Thus, BRAF VE1 IHC may be useful for screening for the BRAF V600E mutation in CRC provided that additional sequencing studies are required to confirm BRAF VE1 antibody-positive cases.