Expression of ephrin receptor A1 on the membrane of epitheliocyte glands of the uterine mucosa in patients with endometrial cancer and endometriosis

Objective: To assess the expression of the Epha1 receptor on the epithelial cell membrane of the glands of the eutopic and ectopic endometrium in women without endometrial pathology, with endometriosis of varying severity and endometrial cancer.

Materials and methods: The study included 46 patients of reproductive age who were treated in the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation from 2020 to 2021. The patients were divided into four groups: Group 1 included 20 women with deep endometriosis (DE), Group 2 included 21 patients with peritoneal endometriosis (PE), Group 3 (comparison group) included 6 patients with endometrial cancer (EC), and Group 4 (control) included 9 patients without endometriosis (no pathological changes in the endometrium) and operated on for tubal-peritoneal infertility factor. The groups were additionally divided into subgroups depending on the phase of the menstrual cycle on the day before the operation. Semi-quantitative evaluation of EphA1 expression on the epithelial cells of the glands of the uterine mucosa was performed by immunohistochemistry, using rabbit polyclonal antibodies ab217363 and the ImageJ open source program for image analysis and processing.

Results: We have shown for the first time that in healthy endometrium, a significantly higher expression of the ephrin receptor EphA1 on the surface of glandular cells is observed in the secretory phase of the menstrual cycle (MC), compared to the proliferative one. The same pattern of receptor expression was found in the eutopic endometrium of patients with PE - higher in the secretory than in the proliferative phases. In the eutopic endometrium of patients with DE, a significantly increased level of EphA1 expression was found in the proliferative and secretory phases of MC compared to patients without endometriosis or with PE. In foci on the peritoneum in both PE and DE, a higher level compared to the norm was found only in the proliferative phase of the cycle. The highest hyperexpressed level was found on the membrane of the glandular cells of the endometrium affected by cancer and in deeply infiltrative foci on the intestine with DE in both phases of the cycle.

Conclusion: Overexpression of the ephrin receptor EphA1 in glandular cells of endometrial tissue in EC and DE makes it a promising target for the development of new technologies for the diagnosis and treatment of these diseases.