Angiogenesis features in patients with melanoma with different BRAf status

Abstract

Neoangiogenesis is an important factor in the development and progression of cancer. Neoangiogenesis in tumors is necessary for its further growth and subsequent metastasis. Intensity ofangiogenesis depends on a balance ofproangiogenic and antiangiogenic factors. One of these angiogenic factors is matrix metalloproteinase-9 (MMP-9) enzyme family endopeptidases participating in the extracellular matrix degradation and remodeling of vessels. It is known that the BRAF V600E mutation can affect the expression ofpro-angiogenic factors in tumor tissue. The purpose of this study was to investigate the microvasculature density in the tumor andperitumoral area in patients with melanoma with different BRAF-status using counting CD-31 positive stained vascular endothelial cells, as well as detection of the expression of matrix metalloprotieinase-9 in tumor cells and cells of microenvironment, followed by analysis of the relationships among these indicators. The material for the study is based on samples of tumor (n = 57) obtainedfrom patients with melanoma. The study revealed that there was a trend to increased angiogenesis in 2-fold (p < 0.05) with the BRAF-positive lentigo melanoma, compared with BRAF-negative patients lentigo melanoma. Vascularization level change was detected, depending on the primary tumor site: the level of vascularization was statistically higher in BRAF-positive patients with localized tumors on the skin of the trunk (p < 0.05), with no significant differences for other important morphologic parameters such as ulceration of the tumor, the severity of lymphocytic infiltration and tumor thickness by Breslow (p > 0.05). No statistically significant differences in the expression of MMP-9 depending on the BRAF-status in the tumor cells and stromal cells in microenvironment (p > 0.05) were detected. Nevertheless, a tendency to an increase in the expression of MMP-9 in the surrounding stroma cells (fibroblasts, lymphocytes, endothelial cells, polymorph nuclear leukocytes, regardless of BRAF-status) was shown. Despite some features of tumor angiogenesis in the skin melanoma patients with different BRAF status angiogenesis in the tumor is influenced by a variety of proangiogenic and antiangiogenic stimulation that are common patterns regardless of BRAF-status.