Interrelation of Steroid Receptor Gene Expression in Uterine Tissues and Serum Concentrations of Immunoregulatory Proteins, Cytokines, Sex Steroids in Proliferative Diseases

Abstract

Pathogenetic mechanisms of uterine leiomyoma, adenomyosis and their combination are complicated and poorly understood, a differential diagnosis of leiomyosarcoma of the uterus is difficult. Our study aimed for a comparative analysis of the serum contents of α2-MG, PAG, some cytokines, sex steroids and the expression of steroid receptor genes in the patients with different variants of uterine proliferative diseases, in order to determine their pathological role, diagnostic and prognostic value. Expression of estrogen receptor genes adenomyosis nodes was 1.5 to 2-fold higher than in leiomyoma, the combined pathology showed intermediate values, and expression of ER and PGR genes in leiomyosarcoma was minimal. In cellular leiomyoma, expression of ER receptor genes in the surrounding myometrium was 2 to 3-fold higher than in cases of simple leiomyomas. At the same time, concentration of estrogen and progesterone in the blood is comparable between the groups and control groups. All the patients have a deficiency of immunomodulatory α2-MG (12-13% for leiomyomas, 20% for adenomyosis, and 23% for malignant pathology). The concentration of immunosuppressive PAG is increased in combined conditions and leiomyosarcoma. In addition, the contents of IL-6 and TNFα increase, the VEGF levels exceed normal values 4 to 4.5-fold, in leiomyoma, 5.5-fold, in combined pathology, 6.5, in adenomyosis, and 10-fold, in leiomyosarcoma.The obtained results confirm that immunomodulatory proteins, cytokines and cell-targeting sex hormones exert an interdependent influence upon each other in the studied diseases, and their significant changes may be used in diagnostics and prognosis.