Distinct Clinical and Pathological Features Are Associated with the BRAFT1799A(V600E) Mutation in Primary Melanoma

The BRAFT1799A mutation encodes BRAFV600E that leads to activation of the mitogen-activated protein kinase pathway. This study aimed to assess the clinico-pathological features of primary invasive melanomas containing the BRAFT1799A mutation. Patients (n=251) with invasive primary melanomas from Australia were interviewed and examined with respect to their melanoma characteristics and risk factors. Independent review of pathology, allele-specific PCR for the BRAFT1799A mutation, immunohistochemical staining with Ki67, and phospho-histone-H3 (PH3) were performed. The BRAFT1799A mutation was found in 112 (45%) of the primary melanomas. Associations with the BRAFT1799A mutation (P<0.05) were as follows: low tumor thickness (odds ratio (OR)=3.3); low mitotic rate (OR=2.0); low Ki67 score (OR=5.0); low PH3 score (OR=3.3); superficial spreading melanoma (OR=10.0); pigmented melanoma (OR=3.7); a lack of history of solar keratoses (OR=2.7); a location on the trunk (OR=3.4) or extremity (OR=2.0); a high level of self-reported childhood sun exposure (OR=2.0); ≤50 years of age (OR=2.5); and fewer freckles (OR=2.5). We conclude that the BRAFT1799A mutation has associations with host phenotype, tumor location, and pigmentation. Although implicated in the control of the cell cycle, the BRAFT1799A mutation is associated with a lower rate of tumor proliferation.