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

Document Type : Research Articles

Authors

1 Division of Surgical Oncology, Department of Surgery, Dr Sardjito Hospital / Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.

2 Department of Pathological Anatomy, Dr Sardjito Hospital / Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.

3 PPDS Ilmu Bedah, Department of Surgery, Dr Sardjito Hospital / Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.

4 PPDS Subspesialis Ilmu Bedah, Department of Surgery, Dr Sardjito Hospital / Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.

5 Department of Surgery, RSUD Banyumas, Banyumas Regency 53192, Indonesia.

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

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