NRASQ61R Immunohistochemistry Detects Both NRASQ61R and KRASQ61R Mutations in Colorectal Cancer

The NRASQ61R monoclonal antibody (clone sp174) is a mutation-specific antibody that is increasingly being used to detect the NRAS mutation in melanomas. This antibody has been reported to be highly correlated with the NRAS mutation status in melanomas and follicular neoplasms of the thyroid gland. However, its utility in colorectal carcinoma (CRC) has remained largely unknown. In this study, we assessed the sensitivity, specificity, and diagnostic utility of NRASQ61R immunohistochemistry in a cohort consisting of tissue sections of 113 CRCs, which were molecularly profiled for the KRAS, NRAS, and BRAF mutations. Five CRCs tested positive for NRASQ61R immunohistochemistry. Four of these CRCs exhibited the NRAS mutation and one exhibited the KRAS mutation. All of the other 108 colorectal carcinomas lacking the NRAS or KRAS mutation tested negative for NRASQ61R immunohistochemistry. In the positively stained cases, we observed a diffuse staining pattern in >90% of the tumour cells with a moderate-to-strong intensity. By contrast, the staining was essentially entirely negative in cases negative for the NRAS or KRAS mutations. We concluded that although it cross-reacts with the mutant KRAS protein, the NRASQ61R antibody is a useful diagnostic tool that assists in the molecular testing of CRCs and facilitates patient management.