PROGNOSTIC VALUE OF IMMUNO-HISTOCHEMICAL MARKERS IN STROMA FOR PROSTATE CANCER AND THEIR INFLUENCE ON MOLECULAR AND BIOLOGYCAL FEATURES OF CANCER CELLS

Prostate cancer (PC) in Ukraine is the second leading malignancy and the most common cancer among men aged 75. In 2006-2016, the morbidity rate of prostate cancer is expected to increase by an average of 14,5% per year. One of the main task in treatment of PC is to prevent the recurrence and disease progression. It requires searching for the prognostic features of the cancer. But PC still remains without International Organization recommendations of molecular biological markers for prognosis and treatment choice. One of the alternation property in estimation of the tumor behavior is the study of reactive changes which is linked to stroma`s cells. The aim of the current study is to improve morpho-logical criteria of prognosis PC by studying the immuno-histochemical markers and significance of the stromal com-ponent in the molded aggressive phenotype of tumor. The basis of morphological and molecular studies have made histological specimens of 40 patients with surgery for PC. Immunohistochemistry using the following monoclo-nal antibodies TGF-β, Е-cadherin, androgen receptor (РА), VEGF, vimentin, CD34, CD4, CD8, CD3, CD20, CD68, smooth muscle actin (α-SMA). PC were distributed into five groups according to Gleason Score (2016) ≤6, 7 (3+4), 7 (4+3), 8, 9-10, and into three groups on the basis of the risk of recurrence (according to recommendations of the European Association of Urologists, 2016). With decrease of differentiation and increase of aggressive clinical behavior of the PC, the stroma was characterized by increase expression of the vimentin (mostly caste by high number of tumor-associated myofibroblasts), increase neoanogiogenesis and infiltration of CD68+ macrophages. The epithelial-mesenchymal transition (EMT) of the cancer cells was investigated. Determined that the appearance of epithelial expression of vementin and reduction of E-cadherin are characteristics for PC with GS 8-10 (р<0,05 and р<0,03 respectively). The following data are revealed: inverse correlation between expression of vimentin and E-cadherin (p<0.05), interrelation between TGFβ and vimentin, and E-cadherin, which indicates the unity of the molecular biological manifestations of EMT and the involvement of the TGFβ in its process. We also demonstrated that from all immunocompe-tent cells (CD68+, CD20+, CD3+, CD4+, CD8+) only mac-rophages are involved in the formation of aggressive pheno-type of PC and it is carried out by the neovascularization, EMT, and associated with tumor progression. Thus higher absolute numbers of CD68+ macrophages in the areas of the greatest infiltration were associated with GS 9-10 (p<0,05) and with group of high risk (p<0,05). In the sites near immu-nocompetent cells infiltration in the periphery of PC the absolute numbers of CD68+ associated with rise of micro-vascular density (p<0,05), expression of VEGF (p<0,05), TGF-β (p<0,05), appearance of vimentin (p<0,05), reduction of E-cadherin (p<0,05), tendency for preservation and rise of expression of androgen receptor (p<0,05) in macrophages. However, it should be noted that because of comparison absolute numbers of CD68+ in the sites of the high immuno-competent cells infiltration and expression of the markers in all tumor no association was found. In this way, a key role of PC stroma in the tumor progression and in formation of its aggressive biological behavior is shown, the participant of stroma in the processes of differentiation decrease and clonal selection of cancer cells, which determine the heterogeneity of cancer and appearance of the focal EMT.