BRAF and NRAS Mutations and the Association with Prognosis of Acral Lentiginous and Nodular Melanomas in Indonesia.

Abstract

Melanomas are rare yet the most aggressive skin cancer among Asians. Clinical presentation, risk factors, and the underlying molecular mechanisms are strikingly different from cutaneous melanoma in Caucasians. Mutation patterns of BRAF and NRAS genes were examined from DNAs derived from primary melanoma tumor tissues (fresh tissues or formalin-fixed paraffin-embedded samples) using pyrosequencing. A total of 63 patients consisting of acral lentiginous melanoma (N=22, 34.9%) and nodular melanoma (N=41, 65.1%) were included in this study. Most patients were diagnosed at Stage III-IV (N=49, 77.8%), Breslow thickness more than 4 mm (N=51, 80.9%), presence of ulceration (N=35, 55.6%), diameter larger than 6 mm (N=61, 96.8%), regional node infiltration (N=41, 77.8%). BRAF and NRAS mutations were found in 28 (44.4%) and 8 (12.7%), respectively. BRAF and NRAS mutations were significantly associated with older melanoma patients (OR = 6.075, 95%CI = 2.013-18.333 dan OR = 13.263, 95%CI = 1.518-115.901, respectively). BRAF mutations were associated with lower overall survival (Median survivals were 16.5 vs 31.4 months, Log-rank test P=0.001). NRAS mutations were not significantly associated with lower overall survival. In this study, melanoma patients are largely diagnosed at the late stages with ulceration and involvement of regional lymph nodes. BRAF mutations are associated with lower survival of cutaneous melanoma patients.