Russian study of morphological prognostic factors characterization in BRAF-mutant cutaneous melanoma

Abstract

Melanoma is one of the aggressive cancer types causing the majority of deaths in skin cancer patients. Mutational screening of the tumor revealed a number of driver mutations in oncogenes which enabled melanoma classification into a few molecular subtypes. BRAF is a key component of mitogen-activated kinase pathway; its activating mutation leads to accelerated melanoma cells proliferation, invasion and survival. Somatic mutations in BRAF were reported in various malignancies, including thyroid cancer, colorectal cancer and melanoma. Specific features of BRAF-positive tumors could have clinical implications as mutational alterations may have an impact on the biological behavior of the tumor and prognosis of the disease.In the present study, the frequency of BRAF V600E mutation was evaluated in Russian patients with melanocytic lesions, of which 41.25% were primary melanoma and 60% were melanocytic nevi. Melanoma patients with trunk localization were of younger age in the BRAF-positive group as compared with BRAF-negative patients. Immunohistochemical evaluations of Ki-67 expression, as well as matrix metalloproteinase-2, -9, were found to be equal in BRAF-positive and BRAF-negative tumors. MMP-2/MMP-9 immunoreactivity was observed in stromal and/or melanocytic cells both in melanoma and nevi patients. Besides tumor cells, MMP-9 expression was observed in lymphocytes in 27.2% of BRAF-positive and in 19.1% of BRAF-negative patients. Histopathological prognostic markers (Breslow thickness, mitotic index, ulceration, tumor infiltrating lymphocytes pattern) did not show any differences depending on BRAF V600E mutational status.The frequency of BRAF-positive melanomas in Russian cohort is similar to other Caucasian population rates. BRAF V600E mutation harboring tumors are more often observed in younger patients without specific features of morphological prognostic factors.