Abstract:

BRAF is a serine/threonine kinase involved in cell cycle progression and proliferation. The V600E point mutation leads to constitutive kinase activity and drives oncogenesis in a large number of melanoma cases. Small Molecule inhibitors were developed to selectively target BRAF V600E mutants and significantly reduced mortality. Thus, establishing BRAF V600E mutational status is critical in clinical management. Molecular methods such as next-generation sequencing (NGS) and real-time or digital droplet PCR are used as the “gold standard”. However, the results of an immunohistochemical (IHC) stain with the anti-BRAF V600E antibody (VE1) are quicker and more cost effective. We used the data from our large volume referral center to identify 1,128 unique cases of primary and metastatic melanoma which had both the VE1 stain and molecular analysis performed. From the data, we found that VE1 had an excellent concordance with molecular methods (sensitivity = 95% and specificity = 99%). We also identified and studied a small number of discrepant cases to understand potential pitfalls such as misinterpreting the presence of heavy pigment deposition or weak positive lesional staining. Our findings confirm that the VE1 stainis reliable method to assess for BRAF V600E mutational status, and has quicker turnaround time, reduced cost, and lower tissue requirements than sequencing methods.