Specifics of VEGF-A, VEGF-C and their receptors levels in the tumor and blood of patients with endometrial cancer depending on the histological type

Background: Serous endometrial carcinoma (SEC) and clear cell endometrial carcinoma (CCC) are rare forms of endometrial cancer (EC) characterized by an aggressive clinical course.

Purpose of the study: Evaluation of differences in the content of vascular endothelial growth factors (VEGF) and their soluble receptors (sVEGF-R) in endometrial tumor tissue and blood of patients with various types of EC.

Materials and methods: The study included 21 patients with CCC (71.5 % with stage I–II, 28.5 % with stage III–IV), as well as 20 patients with SEC (80 % with stage I–II, 20 % with stage III–IV). All had high grade G3 tumors. The control group included patients with endometrioid endometrial carcinoma G3 (EEC): 75 with stage I–II, 25 % with stage III–IV. Samples of intact endometrium obtained from patients who underwent surgical procedures for uterine fibroids (n = 20) and blood samples from conditionally healthy women (n = 20) served as the normal parameters. The levels of VEGF-A, VEGF-C, sVEGF-R1, and sVEGF-R2 were determined by ELISA in 10 % of homogenates of tumor samples, intact endometrium, and blood samples. Statistical processing of the obtained results was performed using the Statistica 10.0 program.

Results: The level of VEGF-A was found to be elevated in tumor samples by 1.8–2 times compared to intact endometrium, and in the blood by 3.8–12 times compared to donor values. The VEGF-A level in the endometrial tissue of cancer patients did not demonstrate a dependence on histology, while in the blood it exhibited a statistically significant increase in patients with rare forms of EC compared to EEC. The sVEGF-R1 levels in the blood and tumor samples were found to exceed standard values, with the highest levels observed in rare forms of EC. The VEGF-A / sVEGF-R1 ratio in EEC did not differ from the normal values, whereas in patients with CCC and SEC, the ratio decreased in tumor samples and increased in the blood compared to donors. The analysis further revealed that the concentration of VEGF-C in the tumor samples was higher than the values observed in the intact endometrium in all cancer patients. However, a statistically significant increase in the level of VEGF-C was observed in CCC and SEC compared to EEC. Conversely, the level of sVEGF-R2 in rare forms of cancer in the tumor was reduced. The level of VEGF-C in the blood of patients with EEC, CCC, and SEC was 1.5–1.6 times higher than that of healthy donors, regardless of the histological structure of endometrial cancer, while sVEGF-R2 did not have reliable differences from healthy donors.

Conclusion: The pronounced activation of sVEGF-R1 and inhibition of sVEGF-R2, as detected in CCC and SEC, suggests that in tumors of rare histological forms of endometrial cancer, along with angiogenesis processes, vasculogenic mimicry occurs, contributing to the aggressiveness of these cancers.

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