VE1 immunohistochemistry accurately detects BRAF V600E mutations in colorectal carcinoma and can be utilized in the detection of poorly differentiated colorectal serrated adenocarcinoma

Serrated adenocarcinoma (SAC) is a recently defined subtype of colorectal carcinoma (CRC). However, in cases where an adjacent serrated adenoma is absent and the differentiation is poor, the diagnosis of SAC can be challenging. BRAF V600E mutation is a characteristic molecular change for the serrated route, but the utility of the newly described BRAF V600E-specific immunohistochemistry in the recognition of SAC is unclear. In this study, we conducted immunohistochemical determination of BRAF V600E mutation and correlated the results to BRAF mutation status and the histological features of SAC in a cohort of 147 CRC patients. There were 13 (8.8 %) BRAF-mutated CRCs confirmed by DNA sequencing. The sensitivity of immunohistochemistry in detecting BRAF V600E mutation was 100 % (13/13) and the specificity was 99.3 % (133/134). Three evaluators independently analyzed the immunohistochemical sections and the correlation between all the evaluators was perfect (kappa = 1). In histologic examination, 33 (22.4 %) of the CRCs were classified as SACs. Twelve of 13 (92.3 %) BRAF-mutated CRCs were evaluated to represent serrated type growth pattern. One of 13 (7.7%) showed poor differentiation not enabling convincing classification. In conclusion, we found immunohistochemistry to be accurate in the detection of the BRAF V600E mutation, with potential applications in the recognition of the BRAF-mutated SACs. Especially in cases where the adjacent adenoma is absent and the tumor is poorly differentiated, BRAF immunohistochemistry could be utilized as an aid to detect SACs.