Pathogenetic mechanisms of benign breast disease development in women of fertile age with endometrial hyperplasia

Proliferative changes in the mammary glands very often associate with gynecological diseases. It is the state of receptors for sex steroids in the tissue but not the absolute concentration of hormones in the blood that influences the development of breast and endometrial diseases. It is still unclear how the structure and properties of estrogen (ER) and progesterone (PR) receptors, associated with ESR1 and PRG gene polymorphisms, change. Thus, a new line of scientific research was the examination of microRNA role in the pathogenesis of benign breast diseases in women of fertile age with endometrial hyperplasia. It is known, that microRNAs are involved in many cellular processes, as they influence target genes. The aim of the study was to determine the prognostic significance of epigenetic markers in benign mammary dysplasia pathogenesis in women of fertile age with endometrial hyperplasia. Materials and Methods. The authors examined 69 women aged 18-49, 27 women with endometrial hyperplasia (EН) without atypia and 42 women with benign mammary dysplasia (BMD) with endometrial hyperplasia without atypia. We studied the expression levels of estrogen and progesterone receptors, and their isoform ratio in the blood serum. We also isolated miR-125b, miR-155, miR-222, and miR-429 by real-time PCR. Results. The prevalence of CC allele of the PvuII C/T polymorphism and GG allele of the Xbal A/G polymorphism in ESR1 gene estrogen receptor causes the BMD in women of fertile age with EH, leading to a decrease in ER sensitivity. Epigenetic changes at the microRNA level indicate a decrease in cell adaptiveness, an increase in their proliferative activity, and an induction of angiogenesis. High expression of miR-155, miR-222, and miR-429 indicates poor prognosis for breast cancer patients. The study of correlation of miR-155, miR-222, and miR-429 with the ESR1 estrogen receptor gene polymorphism showed, that the highest Pvull C/T (TT, TC, and CC) and Xbal A/G (AA, AG, and GG) scores were found in women of fertile age with BMD associated with EH. Conclusion. The results of the molecular genetic studies demonstrate the possibility to predict the occurrence and development of breast proliferative diseases in women of fertile age with endometrial hyperplasia.