ROLE OF STROMAL MICROENVIRONMENT IN THE FORMATION OF INVASIVE, ANGIOGENIC, AND METASTATIC POTENTIAL OF ENDOMETRIOID CARCINOMA OF ENDOMETRIUM.

The aim of the study was to determine the association of indicators of the progression of endometrioid carcinoma of the endometrium (ECE) with the type of stromal microenvironment, the counts of CXCL12+ fibroblasts and CD163+ macrophages, and the expression of the chemokine CXCL12 and its receptor CXCR4 in tumor cells. Histological preparations of ECE samples (n = 51) were analyzed. Expression of CXCL2 and CXCR4 antigens in tumor cells, the content of CXCL12+ fibroblasts and CD163+ macrophages, and the density of microvessels were determined by the immunohistochemical method. Groups of ECE with desmoplastic and inflammatory stromal reactions were delineated. The majority (80.0%) of tumors with desmoplasia were of low differentiation grade, deeply invading the myometrium; 65.0% of patients with these tumors were at stage III of the disease. In ECE cases of stages I-II, 77.4% of ECE showed an inflammatory type of stroma. The high angiogenic and invasive potential of EC of stages I-II was associated with an inflammatory stromal type, high counts of CD163+ macrophages and CXCL12+ fibroblasts in the tumor microenvironment, high expression of the chemokine receptor CXCR4, and reduced expression of its ligand CXCL12 in tumor cells. In the majority of EC of stage III, the increase in angiogenic, invasive, and metastatic potential was accompanied by the presence of desmoplastic stroma, increased expression of CXCR4 in tumor cells, and a high count of CXCL12+ fibroblasts. The obtained results showed that the morphological architecture of the stromal ECE component is related to the molecular features of its constituents and tumor cells. Their interaction modulates the phenotypic characteristics of ECE associated with the degree of malignancy.