The results of immunohistochemical study of signaling pathways’ markers of proliferation in uterine leiomyoma in women using hormonal contraception.

Authors

DOI:

https://doi.org/10.26641/1997-9665.2021.1.67-72

Keywords:

uterine leiomyoma, hormonal contraception, proliferation, IHC markers Ki-67, estrogen (ER) and progesterone (PR) receptors

Abstract

Objective. To elucidate the influence of various components of hormonal contraception in women with uterine leiomyoma (UL) on the key molecular and cellular mechanisms of its proliferation. Methods. Antigen Ki-67, estrogen receptors (ER) and progesterone receptors (PR) were determined by immunohistochemical methods in 230 samples of UL preparations obtained during myomectomy. Depending on the composition of the components of hormonal contraceptives that women used for 12 months before the operation, 8 study groups were created: Group I - control, without the use of any hormonal contraception; Group II - the use of COCs containing 20 μg of ethinylestradiol and 0.075 mg of gestaden; Group III - COCs (30 μg ethinylestradiol and 0.075 mg gestaden) Group IV - COCs (30 μg ethinylestradiol and 0.15 mg desogestrel) Group V - COCs (30 μg ethinyl estradiol and 0.15 mg levonorgestrel) Group VI - COCs (30 μg ethinyl estradiol and 2 mg dienogest) Group VII - COCs (30 μg ethinylestradiol and 3 mg drospirenone) Group VIII - (intrauterine levonorgestrel releasing system (IUD-LNG). Results. In UL samples from group I, an increase of Ki-67 positive cells in 3.4 times was observed (3.1 ± 0.03%; p <0.04) in comparison with intact myometrium (IM) (0.9 ± 0.06%), which is evidence of a higher cell proliferation in the UL, a 3.1-fold increase in the H-index of ER expression - 39.4 ± 4.3 (p <0.05) versus 12.9 ± 1.6 in the group with IM I and in 2.6 times of PR expression - 21.1 ± 1.7 (p <0.05) compared to IM - 8.2 ± 1.4, which may indicate a greater sensitivity of UL to sex hormones and their promoter role in UL proliferation. Expression of Ki-67 in UL samples in women taking COCs, which included dienogest (1.8 ± 0.03%, p <0.05) - group VI and desogestrel (1.9 ± 0.03%, p <0.05) - group IV, was, 42.0% and 38.8% respectively, what ois less than in group I UL, which can be regarded as the cytoprotective effect of the progestogen component of COC on the mitotic activity of UL cells. A positive trend in the expression of Ki-67 persisted when women used COCs containing gestodene (2.1 ± 0.02%; p <0.05) - group III and levonorgestrel (2.2 ± 0.04%, p <0.05) - group V, in which the expression of Ki-67 was shown by a smaller number of PM cells, respectively, by 32.3% and 25.8% than in group I PM, and also to a lesser extent - in group VIII (COC with droperidone), where the mean value of Ki-67 expression in LM samples was 2.6 ± 0.02% and was 16.9% less than in LM group I. An increase in the dose of ethinyl estradiol in COCs from 20 μg (group II) to 30 μg (group III) did not significantly affect the expression of Ki-67, therefore, the content of estrogens in modern low-dose COCs does not contribute to an increase in proliferation in the LM, and the non-contraceptive antiproliferative effect is associated exclusively with biological and the pharmacological properties of individual gestagens in the composition of COCs. It was proved that the studied COCs did not significantly affect the expression of ER and PGR. There was no significant difference in the expression of the Ki-67 marker (2.9 ± 0.04%, p <0.05) in UL cells in women using LNG-IUD for contraception, compared with group I. Conclusion. The results of the study have shown that when choosing a drug for hormonal contraception in women with UL, preference should be given to combined hormonal drugs that contain progestogens with the most pronounced antiproliferative properties (dienogest, desogestrel and levonorgestrel).

References

  1. Kaminsky VV, Potapov VV, Medvedev MV. [The current principle of organ-conserving treatment of women with leiomyoma of the uterus]. Methodical recommendations. 2012. 32 p. Ukrainian.
  2. Manusharova RA. [Modern prolonged methods of contraception in the treatment of uterine fibroids]. Attending physician. 2004;1:62-65. Ukrainian.
  3. Melnik YN. [The choice of a method of contraception in women with uterine fibroids]. Medical aspects of women's health. 2010;7(36):48-53. Ukrainian.
  4. A set of practical recommendations for the use of contraception. Second edition. WHO, Geneva. 2005. 150 p.
  5. [The use of oral contraceptives in women of reproductive age: Ukrainian interdisciplinary consensus]. 2006. 20 p. Ukrainian.
  6. Tatarchuk TF, Shevchuk TV, Bodryagova TF. [Non-contraceptive effects of gestagens - criteria for an individual approach to the appointment of hormonal contraception]. Women's reproductive health. 2006;1(25):177-181. Ukrainian.
  7. Tikhomirov AL, Oleinik CG. [Uterine fibroids and hormonal contraception]. Women's Health. 2008;2(34):90-96. Russian,
  8. Kaunitz AM. Progestin-releasing intrauterine systems and leiomyoma. Contraception. 2007;75(6):130-3.
  9. Pamfamirov YK, Zabolotnov VA, Pamfamirova GL. [Modern views on the etiology, pathogenesis and treatment of uterine fibroids]. Women's health. 2011;5(61):15-20. Ukrainian.
  10. Potapov VO, Donska Y, Medvedev MV. [Histological and immunological assessment of myoma tissue and endometrum in patients with uterine leiomyoma and endometrial hyperplasia]. Morphology. 2014;8(1):80-84. Ukrainian.
  11. Valladares F, Frias I, Bajez D. Characterization of estrogen receptors alpha and beta in uterine leiomyoma. Fertil. Steril. 2006;86(6):1736–1743.
  12. Maruo T, Ohara N. Wang J. Sex steroidal regulation of uterine leiomyoma growth and apoptosis. Hum. Reprod. Update. 2004;10(3):207-220.
  13. Demina TN, Chaika KV, Zhikharsky RV. [Influence of the biological action of progesterone on the processes of apoptosis in the myomatous nodes in women of reproductive age]. Mediko-sotsial'nye problemi sіm'ї. 2013;2(18):43-49. Ukrainian.
  14. Nosenko EN, Skidanova EA. [Progesterone and uterine leiomyoma]. Medical and social problems of the system. 2013;3(18):105-115. Ukrainian.
  15. Blake RE. Leiomyomata uteri: hormonal and molecular determinants of growth. J.Natl.Med.Assoc. 2007;99(10):1170-84.
  16. Maruo T. Progesterone and progesterone receptor modulator in uterine leiomyoma growth. Gynecological Endocrinology. 2007;4:186-187.
  17. Osinsky SP, Gluzman DF, Cliff J, Giese NA. Friss G. [Molecular diagnostics of tumors]. Кiev: DIA; 2007, 248 p. Ukrainian.
  18. Potapov VO, Donska YV, Medvedev MV. [Histological and immunological assessment of myoma tissue and endometrium in patients with uterine leiomyoma and endometrial hyperplasia]. Morphology. 2014;8(1): 80-84. Ukrainian.
  19. Kaminsky VV, Zhuk SI, Grigorenko AN. [Scientific and practical experience of using the levonorgestrel-releasing system: contraceptive and therapeutic effects (literature review)]. Women's health. 2006;28(4):237-246. Ukrainian.
  20. Kosey NV. [Optimization of organ-preserving treatment of uterine leiomyoma using levonorgestrel-releasing system]. Women's health. 2007;3(31):91-98.
  21. Varma R, Sinha D, Gupta JK. Non-contraceptive uses of levonorgestrel-releasing hormone system (LNG-IUS) - a systematic inquiry and overview. Eur. J. Obstet. Gynecol. Reprod. Biol. 2006;125(1):9-28.
  22. Ohara N. Selective estrogen receptor modulator and selective progesterone receptor modulator: therapeutic efficacy in the treatment of uterine leiomyoma. Clin. Exp. Obstet. Gynecol. 2005;32(1):9-11.

Downloads

Published

2021-12-28

How to Cite

Finkova, E. (2021). The results of immunohistochemical study of signaling pathways’ markers of proliferation in uterine leiomyoma in women using hormonal contraception. Морфологія / Morphologia / Morfologìâ, 15(1), 67–72. https://doi.org/10.26641/1997-9665.2021.1.67-72

Issue

Vol. 15 No. 1 (2021)

Section

Статті

License

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

 The authors reserve the right to authorship of their work and transfer to the Journal the right to the first publication of this work under the terms of a license Creative commons Attribution 4.0 International (CC BY 4.0), which allows other people to freely distribute the published work with a mandatory reference to the authors of the original work and the first publication of the work in this journal.
        By submitting a manuscript to the editorial office of the Journal ‘Morphologia’ authors agree to transfer the rights to protect and use the manuscript (all supplemental materials, particularly protected objects such as photos, drawings, diagrams, tables, etc.), including the reproduction in the press and distribution via the Internet; translation of the manuscript into any language; export and import of journal copies with the Authors’ article in order to make it available for public. Authors convey the rights mentioned above to the editorial office without any temporal or territorial limitation all over the world. 
        The Authors guarantee that they have the exclusive rights to use the material transferred to editorial office. Editors are not responsible to third parties for contraventions of warranty given by the Authors. The considered rights are transferred to the editorial office since the moment when the current issue is signed for publishing. Reproduction of materials published in the Journal by other individuals and legal entities is possible only with the consent of Editorial office, with the obligatory indication of the full bibliographic reference of the primary publication. The Authors reserve the right to use the published material, its fragments and parts for teaching materials, oral presentations, dissertation thesis prepararion with obligatory bibliographic citation of the original paper. Electron copy of the published article, downloaded from official journal web-site in .pdf format may be put by authors on the official web-site of their institutions, any other official resources with open access.