Proliferative diseases of the uterus: clinical, immunological, and molecular aspects

Objective. To perform comparative analysis of clinical data, serum levels of acute-phase proteins, cytokines, steroid hormones, and expression of genes encoding sex hormone receptors in tissues of patients with proliferative diseases of the uterus. Patients and methods. We analyzed clinical data of 349 patients with various proliferative diseases of the uterus. We also evaluated their serum levels of α2-macroglobulin, pregnancy-associated α2-glycoprotein, their immunocomplexes with IgG, lactoferrin, VEGF, IL-6, TNFa, IL-8, and sex hormones. Uterine tissue samples were tested for the expression of genes encoding estrogen receptors α and β (ЕRα, ЕRβ) and progesterone receptors (PGR). Data analysis was performed using the statistical packages of SAS 9.4, STATISTICA12, and IBM-SPSS Statistics 22. Results. The changes in the level of acute-phase proteins indicated inflammation. In isolated uterine fibroids, expression of genes encoding progesterone receptors prevailed, whereas in isolated adenomyosis, expression of genes encoding estrogen receptors prevailed. Patients with both uterine fibroids and adenomyosis demonstrated similar levels of expression of genes encoding sex steroid hormone receptors. Tissues of uterine leiomyosarcoma were characterized by downregulated expression of genes encoding sex steroid hormone receptors. Conclusion. Upregulation of genes encoding progesterone receptors in isolated uterine fibroids confirms that therapy with progesterone receptor blockers is appropriate in this case. The predominance of expression of genes encoding estrogen receptors in isolated adenomyosis indicates local hyperestrogenism, justifying the use of progestogens and antiestrogens. Equal expression of genes encoding estrogen and progesterone receptors in patients with combined disease, as wells as high frequency of inflammatory changes in tissues and increased serum levels of inflammatory markers, proves the need for antiinflammatory therapy. Key words: adenomyosis, inflammation, steroid receptor genes, leiomyosarcoma, uterine fibroids, gene expression