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

1005 Background: Mutation in the BRAF gene, predominantly a single base substitution (T1799A), has been found in 66% of malignant melanomas. BRAF (T1799A) encodes an activated form of BRAF (V600E) that leads to activation of the RAS/RAF/MAPK pathway. Despite a large number of studies, the clinical and pathological associations of T1799A in primary melanoma remain poorly understood. The objective of this study was to assess the clinical and pathological features of primary melanomas containing the T1799A mutation. Design: Two hundred and sixty five patients with 267 primary melanomas from Victoria, Australia, nested within a larger study, were prospectively interviewed and examined with respect to their melanoma characteristics and risk factors. Independent histopathologic reviews were performed on all specimens. All primary melanomas were screened with allele-specific PCR for the T1799A mutation. The allele-specific PCR technique allows for detection of 2% mutant DNA when mixed with wild type DNA. Results: Of 267 tumour samples, 253 (95%) samples were successfully amplified. The T1799A mutation was found in 114 (45%) of the primary melanomas. Univariate analysis revealed that the following parameters were associated with the T1799A mutation: 1) low tumour thickness ( 4mm, OR 0.3, 95% CI 0.1-0.7); 2) low mitotic index ( =10/ mm2, OR 0.5, 95% CI 0.2-1.0); 3) superficial spreading melanoma (SSM) (SSM, OR 1.0, REF; lentigo maligna melanoma, OR 0.1, 95% CI 0.1-0.4; nodular melanoma, OR 0.5, 95% CI 0.3-1.0); 4) pigmented melanoma (amelanotic melanoma, OR 1.0, REF; pigmented melanoma OR 3.8, 95% CI 1.8-8.0); 5) intermittently sun-exposed sites (chronically sun-exposed sites, OR 1.00, REF; intermittently sun-exposed sites OR 2.5, 95% CI 1.4-4.8); 6) younger age (