PECULIARITIES OF c-Myc PROTEIN EXPRESSION IN ENDOMETRIAL CARCINOMAS WITH SIGNS OF AN AGGRESSIVE COURSE OF THE DISEASE

Brieieva O.V., Nesina I.P., Iurchenko N.P., Buchynska L.G.

• R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine

Endometrial cancer (EC) is characterized by marked clinical and morphological heterogeneity and variability of the course of the disease, which necessitates the search for molecular biological markers that most accurately reflect the aggressiveness of the tumor. The c-Myc protein is considered to be one of the promising markers, and therefore, a detailed study of its role in determining the malignant potential of endometrial cancer is relevant. Aim: to determine the association of c-Myc protein expression in endometrial carcinomas with such indicators of the aggressive course of the malignant process as proliferative activity, expression of epithelial-mesenchymal transition markers and ploidy of tumor cells. Object and methods: The study was conducted on tumor tissue samples from 55 patients with FIGO I–II stage of the endometrial carcinoma. Marker expression was assessed immunohistochemically using primary antibodies to c-Myc, E2F1, E-cadherin, beta-catenin and vimentin proteins by calculating the label index (LI), which reflects the percentage of positively stained cells. The DNA content and proliferative potential of tumor cells were evaluated by flow cytometry, determining the DNA index (iDNA) and proliferation index (PI, %), respectively. Results: A positive correlation between the expression of c-Myc protein and transcription factor E2F1, which controls the transition from G1-to the S-phase of the cell cycle (r = 0.58; p < 0.05), was determined. It was found that in tumors with a high level of c-Myc (LI > 10.0%), more intensive proliferation is observed than in carcinomas with a low level of this marker (PI 33.4 ± 2.5 and 26.1 ± 2.4% respectively; p < 0.05). No significant differences were found in the expression level of adhesion proteins for E-cadherin and beta-catenin in carcinomas with high and low levels of c-Myc. At the same time, it was found that the expression of the vimentin mesenchymal cell marker was lower in carcinomas with a high level of c-Myc compared with tumors with a low level (LI 20.7 ± 6.4 and 44.6 ± 6.2%, respectively; p < 0, 05). There was an increase in c-Myc expression in aneuploid tumors compared with diploid (LI 20.8 ± 9.1 and 6.7 ± 2.2%, respectively; p < 0.05), which was associated with a low degree of differentiation and deep tumor invasion in myometrium. Conclusion: High expression of c-Myc protein in endometrial carcinomas is associated with increased proliferative activity, signs of an incomplete epithelial-mesenchymal transition and aneuploid status of tumors, which indicates the important role of this protein in the progression of the malignant process in the endometrium and may become the basis for its use for identifying tumors with more aggressive potential.