. Prevalence and prognostic mutation V600E in the BRAF gene in stage I cutaneous melanoma

Abstract

Introduction. Melanoma is one of the most aggressive skin tumors, which occurs against the background of malignant transformation and proliferation of melanocytes. Risk factors for the development of cutaneous melanoma are solar radiation and duration of exposure, old age, individual patient characteristics (light skin, a large number of nevi, including atypical ones, family history) and others. Research in recent years shows that this disease is associated with a number of genetic changes, both congenital and acquired.Aim. To study the frequency of occurrence and prognostic significance of the V600E mutation in the BRAF gene in stage I skin melanoma.Materials and methods. The study was retrospective in nature and included 88 patients with stage I cutaneous melanoma (pT1–2aN0M0). All patients underwent a sentinel lymph node biopsy and no metastases were detected in it (pN0). All patients underwent molecular genetic analysis of the tumor to identify the V600E mutation in the BRAF gene with further assessment of the effect on the progression of early skin melanoma in cases of its detection.Results. The median follow-up time for patients was 32.5 (12–214) months. In 25 (28.4 %) patients of the total sample, the V600E mutation in the BRAF gene was detected. Melanoma progression during follow-up occurred in 23.9 % of patients: 44 % with the V600E mutation in the BRAF gene and 15.9 % without it (p = 0.012). In patients with this mutation, regional metastasis was more often observed, with a predominant localization of distant metastases in the bones. Survival rates were significantly higher in patients without a mutation in the BRAF gene: 1-year disease-free survival of patients without a mutation in this gene was 95 %, 3-year – 87%, 5-year – 65 %, in patients with this mutation – 84, 57 and 37 % respectively. According to the results of Cox regression analysis, in the presence of a mutation in the BRAF gene, there was an increase in the risk of progression to stage I cutaneous melanoma by 2.973 times (p = 0.016).Conclusion. The V600E mutation in the BRAF gene occurs in 28.4 % of patients with stage I cutaneous melanoma and is an unfavorable prognostic factor for disease progression.