Uterine myoma and adenomyosis: molecular characterization by steroid receptor gene expression
Objective. To study the characteristics of endometrial and myometrial responses to steroid stimulation by determining the level of steroid receptor gene expression in the myomatous nodules, adenomyosis, and the surrounding myometrium in uterine myoma, combined and isolated adenomyosis.Shramko S.V., Gulyaeva L.F., Bazhenova L.G., Levchenko V.G.
Material and methods. Steroid receptor gene expression was comparatively analyzed in 48 patients with cellular myoma (n = 11), simple myoma (n = 15), adenomyosis (n = 12), and myoma concurrent with adenomyosis (n = 10). The investigators used uterine tissue samples removed during surgery, such as those of myomatous nodules, adenomyosis and their surrounding myometrium. The expression level of the studied genes was determined using real-time PCR. The latter employed sequence-specific primers for estrogen receptor and progesterone receptor genes.
Results. The level of steroid receptor gene expression in the nodules was 2-9 times greater than that in the myometrium. There was the highest expression of estrogen receptor genes in the nodules of patients with adenomyosis and the lowest one in those with simple myoma. The expression of progesterone receptor genes in the nodules and myometrium was determined to be highest in patients with cellular myoma and to be lowest in those with adenomyosis.
Conclusion. The foci of adenomyosis were characterized by the high expression of estrogen receptor genes with the insufficient expression of progesterone receptor genes. The significantly high level of estrogen receptor gene expression in the myometrium of patients with cellular myoma may have important pathogenetic value, by determining recurrence rates and propensity. The concurrent pathology was characterized by the equivalent and low expression of steroid receptor genes, which can explain the lack of therapeutic effects. The findings will assist in personifying therapeutic approaches to choosing treatment policy for patients with both combined and isolated benign proliferative uterine diseases.
Keywords
adenomyosis
uterine myoma
cellular uterine myoma
concurrent pathology
estrogen receptor genes
progesterone receptor genes
steroid receptor gene expression
Supplementary Materials
References
1. Kim J.J., Sefton E.C. The role of progesterone signaling in the pathogenesis of uterine leiomyoma. Mol. Cell. Endocrinol. 2012; 358(2): 223-31. doi: 10.1016/j.mce.2011.05.044.
2. Буянова С.Н., Юдина Н.В., Гукасян С.А., Мгелиашвили М.В. Современные аспекты роста миомы матки. Российский вестник акушера-гинеколога. 2012; 12(4): 42-8. [Buyanova S.N., Yudina N.V., Gukasian S.A., Mgeliashvili M.V. Uterine myoma growth: Current aspects. Rossiiskiivestnik akushera-ginekologa/Russian Bulletin of Obstetrician-Gynecologist. 2012; 12(4): 42-8. (in Russian)]
3. Duhan N., Sirohiwal D. Uterine myomas revisited. Eur. J. Obstet. Gynecol. Reprod. Biol. 2010; 152(2): 119-25. doi: 10.1016/j.ejogrb.2010.05.010.
4. Manta L., Suciu N., Toader O., Purcărea R.M., Constantin A., Popa F. The etiopathogenesis of uterine fibromatosis. J. Med. Life. 2016; 9(1): 39-45.
5. Дамиров М.М. Современная тактика ведения больных с аденомиозом. М.: Издательство БИНОМ; 2015. 111с. [Damirov M. Modern tactics of managing patients with adenomyosis. Moscow: Publishing house BINOM; 2015. 111p. (in Russian)]
6. Печеникова В.А., Акопян Р.А., Кветной И.М. К вопросу о патогенетических механизмах развития и прогрессии внутреннего генитального эндометриоза – аденомиоза. Журнал акушерства и женских болезней. 2015; 64(6): 51-7. [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 zhenskih boleznej/Journal of Obstetrics and Women’s Diseases. 2015; 64(6): 51-7. (in Russian)]
7. Унанян А.Л., Сидорова И.С., Коган Е.А. Активный и неактивный аденомиоз: клинико-морфологические варианты развития, дифференцированный подход к терапии. Акушерство, гинекология и репродукция. 2012; 6(2): 25-30. [Unanyan A.L., Sidorova I.S., Kogan E.A.Active and inactive adenomyosis: clinical and morphological variants of development, differentiated approach to therapy. Akusherstvo, ginekologiya, reproduktologiya/Obstetrics, gynecology, reproductology. 2012; 6(2): 25-30. (in Russian)]
8. Сидорова И.С., Унанян А.Л., Агеев М.Б., Ведерникова Н.В., Жолобова Н.М. Современное состояние вопроса о патогенезе, клинике, диагностике и лечении миомы матки у женщин репродуктивного возраста. Акушерство, гинекология и репродукция. 2012; 6(4): 22-8. [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, reproduktologiya/ Obstetrics, gynecology, reproduction. 2012; 6(4): 22-8. (in Russian)]
9. Печеникова В.А. К вопросу о нозологической значимости и правомочности использования термина «Эндометриоидная болезнь». Журнал акушерства и женских болезней. 2012; 61(5): 122-31. [Pechenikova V.A. To the question of nosological significance and eligibility of using the term “Endometriosis”. Zhurnal akusherstva i zhenskih boleznej/Journal of Obstetrics and Women’s Diseases. 2012; 61(5): 122-31. (in Russian)]
10. Leyendecker G., Kunz G., Noe M., Herberts M., Mall G. Endometriosis: a dysfunction and disease of the archimetra. Hum. Reprod. Update. 1998; 4(5):752-62.
11. Noe M., Kunz G., Herberts M., Mall G., Leyndecker G. The cyclic pattern of the imminocytochemical expression of estrogen and progesterone receptors inhuman myometrial and endometrial layers: characterisation of the endometrial-subendometrial unit. Hum. Reprod. 1999; 14(1): 190-7.
12. Leyendecker G., Bilgicyildirim A., Inacker M., Stalf T., Huppert P., Mall G. et al. Adenomyosis and endometriosis. Re-visiting their association and further insights into the mechanisms of auto-traumatisation. An MRI study. Arch. Gynecol. Obstet. 2015; 291(4): 917-32. doi: 10.1007/s00404-014-3437-8.
13. Тихомиров А.Л., Манухин И.Б., Сарсания С.И. Миома матки в сочетании с эндометриозом и гиперплазией эндометрия. Как лечить? Российский вестник акушера-гинеколога. 2014; 14(3): 76-8. [Tihomirov F.L., Manuhin I.B., Sarsaniy S.I. Uterine fibroid sin conjunction with endometriosis and endometrial hyperplasia. How to treat? Rossiiskii vestnik akushera-ginekologa/Russian Bulletin of Obstetrician-Gynecologist. 2014; 14(3): 76-8. (in Russian)]
14. Kaba M., Tokmak A., Timur H., Özdal B., Şirvan L., Güngör T. A rare case of leiomyosarcoma originating from the left round ligament of the uterus. J. Exp. Ther. Oncol. 2016; 11(3): 237-40.
15. Ishikawa H., Ishi K., Serna V.A., Kakazu R., Bulun S.E., Kurita T. Progesterone is essential for maintenance and growth of uterine leiomyoma. Endocrinology. 2010; 151(6): 2433-42. doi: 10.1210/en.2009-1225.
16. Савицкий Г.А. Роль локальной гиперэсрадиолемии в патогенезе возникновения и роста миомы. Журнал акушерства и женских болезней. 2009; 58(4): 79-92. [Savickiy G.A. The role of local hyperestradiolia in the pathogenesis of the onset and growth of fibroids. Zhurnal akusherstva i zhenskih boleznej/Journal of Obstetrics and Women’s Diseases. 2009; 58(4): 79-92. (in Russian)]
17. Гуриев Т.Д., Сидорова И.С., Унанян А.Л. Сочетание миомы матки и аденомиоза. М.: МИА; 2012. 251с. [Guriev T.D., Sidorova I.S., Unanyan A.L. Combination of uterine fibroids and adenomyosis. Moscow: MIA; 2012. 251p. (in Russian)]
18. Steven H., Eisinger S.H., Meldrum S., Fiscella K., le Roux H.D., Guzick D.S. Low-dose mifepristone for uterine leiomyomata. Obstet. Gynecol. 2003; 101(2): 243-50.
19. Takeuchi A., Koga K., Miyashita M., Makabe T., Sue F., Harada M. et al. Dienogest reduces proliferation, NGF expression and nerve fiber density in human adenomyosis. Eur. J. Obstet. Gynecol. Reprod. Biol. 2016; 207: 157-61. doi: 10.1016/j.ejogrb.2016.10.053.
20. Савицкий Г.А., Савицкий А.Г. Миома матки (проблемы патогенеза и патогенетической терапии). СПб.: ЭЛБИ; 2000. 235с. [Savitsky G.A., Savitsky A.G. Myoma of the uterus (problems of pathogenesis and pathogenetic therapy). St. Petersburg: ELBI; 2000. 235p. (in Russian)]
21. Стрижаков А.Н., Давыдов А.В., Пашков В.М, Лебедев В.А. Доброкачественные заболевания матки. М.: ГЭОТАР-Медиа; 2014. 304с. [Strizhakov A.N., Davydov A.V., Pashkov V.M., Lebedev V.A. Benign uterine disease. Moscow: GEOTAR-Media; 2014. 304p. (in Russian)]
Received 17.07.2017
Accepted 22.09.2017
About the Authors
Shramko Svetlana Vladimirovna, PhD (medical science), Associate Professor of Teaching assistant of Department of obstetrics and gynecology,Novokuznetsk State Institute for Postgraduate Training of Physicians; Branch, Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia.
654005, Russia, Novokuznetsk, Stroiteley str. 5. Tel.: +73843324750. E-mail: shramko_08@mail.ru
Lyudmila Fedorovna Gulyaeva, PhD (Doctor of Biology), Professor, Institute of Molecular Biology and Biophysics.
630117, Russia, Novosibirsk, Timakov str. 2/12. Tel.: +73833064444. E-mail: gulyaeva@niimbb.ru
Bazhenova Lyudmila Grigoryevna, M.D. (Doctor of medical science), Professor, Head of Department of obstetrics and gynecology, Novokuznetsk State Institute
for Postgraduate Training of Physicians; Branch, Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia.
654005, Russia, Novokuznetsk, Stroiteley str. 5. Tel.: +73843324768. E-mail: l_bagenova@mail.ru
Levchenko Vladimir Grigorevich, PhD (medical science), Associate Professor of Teaching assistant of Department of Department of obstetrics and gynecology,
Novokuznetsk State Institute for Postgraduate Training of Physicians; Branch, Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia.
654005, Russia, Novokuznetsk, Stroiteley str. 5. Tel.: +73843324750. E-mail: vglev@yandex.ru
For citations: Shramko S.V., Gulyaeva L.F., Bazhenova L.G., Levchenko V.G. Uterine myoma and adenomyosis: molecular characterization by steroid receptor gene expression. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (4): 58-63. (in Russian)
https://dx.doi.org/10.18565/aig.2018.4.58-63
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