INTERRELATION OF STEROID RECEPTOR GENE EXPRESSION IN UTERINE TISSUES AND SERUM CONCENTRATIONS OF IMMUNOREGULATORY PROTEINS, CYTOKINES, SEX STEROIDS IN PROLIFERATIVE DISEASES
https://doi.org/10.15789/1563-0625-2018-5-731-738
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.
About the Authors
S. V. ShramkoRussian Federation
PhD (Medicine), Associate Professor, Department of Obstetrics and Gynecology.
Novokuznetsk.V. N. Zorina
Russian Federation
PhD, MD (Biology), Main Research Associate, Research Laboratory of Immunology.
Novokuznetsk.N. A. Zorin
Russian Federation
PhD, MD (Biology), Professor, Head, Research Laboratory of Immunology.
Novokuznetsk.I. A. Botvinyeva
Russian Federation
PhD (Biology), Head, Clinical Diagnostic Laboratory.
Novokuznetsk.S. V. Arkhipova
Russian Federation
PhD (Medicine), Senior Research Associate, Research Laboratory of Immunology.
Novokuznetsk.V. V. Likhacheva
Russian Federation
PhD (Medicine), Assistant Professor, Department of Obstetrics and Gynecology.
Novokuznetsk.References
1. Baryshnikov A.Yu., Shishkin Yu.V. Programmed cell death (apoptosis). Rossiyskiy onkologicheskiy zhurnal = Russian Cancer Journal, 1996, no. 1, pp. 64-66. (In Russ.)
2. Guriev T.D., Sidorova I.S., Unanyan A.L. Combination of uterine fibroids and adenomyosis. Moscow: Moscow News Agency, 2012. 251 p.
3. Zorin N.A., Zorina V.N. Evolution of macroglobulin family proteins – from bacteria to primates. Zhurnal evolyutsionnoy biokhimii i fiziologii = Journal of Evolutionary Biochemistry and Physiology, 2017, Vol. 53, no. 6, pp. 389-397. (In Russ.)
4. Levchenko V.G., Zorina V.N., Bazhenova L.G., Zorina R.M., Zorin N.A. Some aspects of preeclampsia pathogenesis at pregnancy. Rossiyskiy vestnik akushera-ginekologa = Russian Bulletin of Obstetrician-Gynecologist, 2010, Vol. 10, no. 3, pp. 21-25. (In Russ.)
5. Pechenikova V.A., Akopyan R.A., Kvetnoy I.M. To a question of pathogenetic mechanisms of development and a progression of internal genital endometriosis – an adenomyosis. Zhurnal akusherstva i zhenskikh bolezney = Journal of Obstetrics and Women’s Diseases, 2015, Vol. LXIV, issue 6, pp. 51-57. (In Russ.)
6. Rodionova M.V., Vorotnikov I.K., Rodionov V.V., Chkhivadze N.V., Dudko E.A., Ryabchikov D.A., Oshkina E.V., Bogush T.A. Role of estrogen receptor beta in the development ant treatment of breast cancer. Rossiyskiy bioterapevticheskiy zhurnal = Russian Biotherapeutical Journal, 2015, Vol. 14, no. 2, pp. 39-46. (In Russ.)
7. Sidorova I.S., Unanyan A.L., Ageev M.B., Vedernikova N.V., Zholobova N.M. The current state of the issue of the pathogenesis, clinic, diagnosis and treatment of uterine fibroids in women of reproductive age. Akusherstvo, ginekologiya, reproduktsiya = Obstetrics, Gynecology, Reproductology, 2012, Vol. 6, no. 4, pp. 22-28. (In Russ.)
8. Strizhakov A.N., Davydov A.V., Pashkov V.M., Lebedev V.A. Benign uterine diseases. Moscow: GEOTAR-Media, 2014. 304 p.
9. Sysoev K.A., Kulagina N.V., Totolian A.A. Cytokine expression profiles of peritoneal fluid in patients with uterine leiomyoma. Meditsinskaya immunologiya = Medical Immunology (Russia), 2006, Vol. 8, no. 4, pp. 547-556. doi: 10.15789/1563-0625-2006-4-547-556.
10. Cui R.R., Wright J.D., Hou J.Y. Uterine leiomyosarcoma: a review of recent advances in molecular biology, clinical management and outcome. BJOG, 2017, Vol. 124, no. 7, pp. 1028-1037.
11. Foca C., Moses E.K., Quinn M.A., Rice G.E. Differential expression of the alpha(2)-macroglobulin receptor and the receptor associated protein in normal human endometrium and endometrial carcinoma. Mol. Hum. Reprod., 2000, Vol. 6, no. 10, pp. 921-927.
12. Kobayashi H., Uekuri C., Akasaka J., Ito F., Shigemitsu A., Koike N., Shigetomi H. The Biology of uterine sarcomas: A review and update. Mol. Clin. Oncol., 2013, Vol. 1, no. 4, pp. 599-609.
13. Manta L., Suciu N., Toader O., Purcărea R.M. Constantin A., Popa F. The etiopathogenesis of uterine fibromatosis. J. Med. Life., 2016, Vol. 9, no. 1, pp. 39-45.
14. Plewka D., Marczyński J., Morek M., Bogunia E., Plewka A. Receptors of hypothalamic-pituitary-ovarianaxis hormone in uterine myomas. Biomed. Res. Int., 2014, Vol. 2014, 521313. doi: 10.1155/2014/521313.
15. Zhang Q., Ubago J., Li L., Guo H., Liu Y., Qiang W., Kim J.J., Kong B., Wei J.J. Molecular analyses of 6 different types of uterine smooth muscle tumors: Emphasis in atypical leiomyoma. Cancer, 2014, Vol. 120, no. 20, pp. 3165-3177.
Review
For citations:
Shramko S.V., Zorina V.N., Zorin N.A., Botvinyeva I.A., Arkhipova S.V., Likhacheva V.V. INTERRELATION OF STEROID RECEPTOR GENE EXPRESSION IN UTERINE TISSUES AND SERUM CONCENTRATIONS OF IMMUNOREGULATORY PROTEINS, CYTOKINES, SEX STEROIDS IN PROLIFERATIVE DISEASES. Medical Immunology (Russia). 2018;20(5):731-738. (In Russ.) https://doi.org/10.15789/1563-0625-2018-5-731-738