Distinct clinical and pathological features are associated with the BRAF T1799A(V600E) mutation in primary melanoma

The BRA(T1799A) mutation encodes BRAF(V600E) 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 BRAF(T1799A) 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 BRAF(T1799A) mutation, immunohistochemical staining with Ki67, and phospho-histone-H3 (PH3) were performed. The BRA fall 799A mutation was found in 112 (45%) of the primary melanomas. Associations with the BRAF(T1799A) mutation (P < 0.05) were as follows: low tumor thickness (odds ratio (OR) =33); 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 yearsof age (OR =2.5); and fewer freckles (OR -2.5). We conclude that the BRA rl 799A mutation has associations with host phenotype, tumor location, and pigmentation. Although implicated in the control of the cell cycle, the BRAF(T1799A) mutation is associated with a lower rate of tumor proliferation.