Expression of chemokine receptor CXCR4 in tumor cells and content of CXCL12+-fibroblasts in endometrioid carcinoma of endometrium.

Abstract

The expression of the CXCL12chemokine and its receptor CXCR4in the stromal component of the tumor plays an important role in tumor cell migration, proliferation, inhibition of apoptosis and determination of invasive and metastatic potential of malignant neoplasms of various genesis. The significance of CXCL12and CXCR4expression in endometrial tumor cells for cancer progression is not fully understood. To evaluate the content of CXCL12+-fibroblasts and expression of CXCL12and CXCR4in endometrial cancer cells, depending on the tumor stage. Surgical material of 45patients with endometrioid carcinoma of the endometrium (ECE) of the stages I-II and III was studied using morphological and immunohistochemical methods. In ECE of stage I-II CXCR4expression was lower (43.3± 4.2%) while CXCL12expression was higher (33.6± 2.4%) compared with the corresponding indices​​ in ECE of stage III (63.6± 3.5%, 24.5± 1.9%, respectively, p< 0.05). In ECE of stage III, high expression of CXCR4 (> Me) and low CXCL12 (< Me) was observed in 80% of samples; these tumors invaded more than 1/2of the myometrium. There was a positive correlation between the depth of tumor invasion in the myometrium and the presence of metastases and CXCR4expression in tumor cells (R= 0.5and R= 0.4, respectively, p< 0.05) and the negative correlation with the expression of CXCL12 (R= -0.6and R= -0.3, respectively, p< 0.05). In tumors that deeply invaded the myometrium, a high number of the CXCL12+-fibroblasts (> Me) (14.9± 1.3%) was detected. The obtained data reflect the communication of the immunosuppressive factor of the tumor microenvironment, i.e. CXCL12+-fibroblasts and CXCR4expressing tumor cells. We suggest that the aggressiveness of ECE is determined by the combined effect of these two factors.