Angiogenesis features in patients with melanoma with different BRAf status

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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.

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About the authors

Maria B. Aksenenko

Krasnoyarsk State Medical University n.a. prof. V.F. Voyno-Yasenetsky

Email: aksenenko_mariya@mail.ru
Krasnoyarsk, 660022, Russian Federation
MD, PhD, docent, Department of Pathophysiology with a Course of a Clinical Pathophysiology, Krasnoyarsk State Medical University of prof. V.F. Voyno-Yasenetsky

T. G Ruksha

Krasnoyarsk State Medical University n.a. prof. V.F. Voyno-Yasenetsky

Krasnoyarsk, 660022, Russian Federation
Department of Pathophysiology with a course of clinical pathophysiology

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Copyright (c) 2017 Aksenenko M.B., Ruksha T.G.

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