Morphologic determinants of recurrent endometrial polyps in women of reproductive age
AbstractEndometrial polyps are a common nosology that, although often asymptomatic, is associated with reproductive dysfunction. Hysteroresectoscopic removal of polyps is an effective treatment, but recurrence is not uncommon. The recurrence rate after polypectomy according to different studies varies from 13 to 43%. As predisposing factors, such characteristics as hyperplastic type of polyps, a larger initial number of polyps and the duration of dynamic follow-up are emphasized. A detailed analysis of the histological features of the removed polyps will optimize the management of patients after polypectomy for the timely detection and treatment of recurrences.
The aim of the study was to expand the understanding of the pathogenesis of recurrent endometrial polyps in women of reproductive age.
Material and methods. 94 women with primary endometrial polyps [median age 37.58 years (Q1–Q3: 33.543–40.242)] and 96 women with endometrial polyp recurrence [median age 36 years (Q1–Q3: 34.30–37.99)] were included in a prospective cohort comparative open study. We collected anamnesis, anthropometric data, performed sonographic examination of the pelvic organs, hysteroscopy of the uterine cavity with targeted biopsy of the endometrium, morphologic and immunohistochemical examination.
Results. The expression level of the CD138 marker in the recurrent polyp group was 8 times higher compared to the primary polyp group, and the CD20 marker was 1.5 times higher (p<0.001).
Conclusion. Abnormal expression of CD138 and CD20 in the basal layer of the endometrium indicates the persistence of inflammation as a key factor in the development of endometrial polyp recurrence.
Keywords: endometrial polyps; recurrence; immunohistochemical
Funding. The study had no sponsor support.
Conflict of interest. The authors declare no conflict of interest.
For citation: Orazov M.R., Mihaleva L.M., Poimanova O.F. Morphologic determinants of recurrent endometrial polyps in women of reproductive age. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2024; 12 (3): 55–60. DOI: https://doi.org/10.33029/2303-9698-2024-12-3-55-60 (in Russian)
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30. Sheng K.K., Lyons S.D. To treat or not to treat? An evidence-based practice guide for the management of endometrial polyps. Climacteric. 2020; 23: 336–42. DOI: https://doi.org/10.1080/13697137.2020.1742107
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Анализ показал, что для рецидивирующих полипов характерны более высокие уровни экспрессии иммуногистохимических маркеров CD138 и CD20 по сравнению с группой первичных полипов. Полученные результаты подтверждают гипотезу о тесной патогенетической связи между развитием ХЭ и рецидивированием эндометриальных полипов после хирургического лечения. Повышенная экспрессия маркеров В-лимфоцитов и плазматических клеток (CD20 и CD138), а также выраженные признаки фиброзно-склеротической трансформации эндометрия могут рассматриваться в качестве предикторов рецидивирования заболевания.
Заключение
Результаты исследования позволяют сделать вывод о том, что ключевую роль в патогенезе рецидивирующих ПЭ играет персистенция воспаления в базальном слое эндометрия. Данное заключение подтверждается обнаруженной аномальной экспрессией маркеров CD138 и CD20 в ткани полипов, что свидетельствует о наличии субпопуляции аберрантных клеток, способных избегать физиологических механизмов регуляции и приводить к рецидиву патологического процесса.
Таким образом, полученные результаты углубляют понимание молекулярных основ развития рецидивирующих ПЭ и открывают перспективы для разработки новых диагностических и терапевтических подходов, направленных на элиминацию воспаления из базального эндометрия. Дальнейшие исследования в этом направлении позволят оптимизировать тактику ведения пациенток с данным заболеванием и улучшить отдаленные результаты лечения.
Литература
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8. Gu F., Zhang H., Ruan S., Li J., Liu X., Xu Y. et al. High number of endometrial polyps is a strong predictor of recurrence: findings of a prospective cohort study in reproductive-age women // Fertil. Steril. 2018. Vol. 109, N 3. P. 493-500.
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12. Cicinelli E., Vitagliano A., Loizzi V., De Ziegler D., Fanelli M., Bettocchi S. et al. Altered gene expression encoding cytochines, grow factors and cell cycle regulators in the endometrium of women with chronic endometritis // Diagnostics (Basel). 2021. Vol. 11, N 3. P. 471. DOI: https://doi.org/10.3390/diagnostics11030471
13. Kitaya K., Takeuchi T., Mizuta S., Matsubayashi H., Ishikawa T. Endometritis: new time, new concepts // Fertil. Steril. 2018. Vol. 110. P. 344-350. DOI: https://doi.org/10.1016/j.fertnstert.2018.04.012
14. Puente E., Alonso L., Laganà A.S., Ghezzi F., Casarin J., Carugno J. Chronic endometritis: old problem, novel insights and future challenges // Int. J. Fertil. Steril. 2020. Vol. 13. P. 250-256.
15. Kasius J.C., Fatemi H.M., Bourgain C., Sie-Go D.M., Eijkemans R.J., Fauser B.C. et al. The impact of chronic endometritis on reproductive outcome // Fertil. Steril. 2011. Vol. 96. P. 1451-1456. DOI: https://doi.org/10.1016/j.fertnstert.2011.09.039
16. Cicinelli E., Haimovich S., De Ziegler D., Raz N., Ben-Tzur D., Andrisani A. et al. MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining // J. Assist. Reprod. Genet. 2022. Vol. 39. P. 219-226. DOI: https://doi.org/10.1007/s10815-021-02356-1
17. Song D., Li T.C., Zhang Y., Feng X., Xia E., Huang X. et al. Correlation between hysteroscopy findings and chronic endometritis // Fertil. Steril. 2019. Vol. 111. P. 772-779. DOI: https://doi.org/10.1016/j.fertnstert.2018.12.007
18. Moreno I., Cicinelli E., Garcia-Grau I., Gonzalez-Monfort M., Bau D., Vilella F. et al. The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology // Am. J. Obstet. Gynecol. 2018. Vol. 218. P. 602.e1-602.e16. DOI: https://doi.org/10.1016/j.ajog.2018.02.012
19. Chen P., Chen P., Guo Y., Fang C., Li T. Interaction between chronic endometritis caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure // Front. Immunol. 2021. Vol. 12. Article ID 748447. DOI: https://doi.org/10.3389/fimmu.2021.748447
20. Chen W., Wei K., He X., Wei J., Yang L., Li L. et al. Identification of uterine microbiota in infertile women receiving in vitro fertilization with and without chronic endometritis // Front. Cell Dev. Biol. 2021. Vol. 9. Article ID 693267. DOI: https://doi.org/10.3389/fcell.2021.693267
21. García-Peñarrubia P., Ruiz-Alcaraz A.J., Martínez-Esparza M., Marín P., Machado-Linde F. Hypothetical roadmap towards endometriosis: prenatal endocrine-disrupting chemical pollutant exposure, anogenital distance, gut-genital microbiota and subclinical infections // Hum. Reprod. Update. 2020. Vol. 26. P. 214-246. DOI: https://doi.org/10.1093/humupd/dmz044
22. Kobayashi H., Higashiura Y., Shigetomi H., Kajihara H. Pathogenesis of endometriosis: the role of initial infection and subsequent sterile inflammation (review) // Mol. Med. Rep. 2014. Vol. 9. P. 9-15. DOI: https://doi.org/10.3892/mmr.2013.1755
23. Indraccolo U., Di Iorio R., Matteo M., Corona G., Greco P., Indraccolo S.R. The pathogenesis of endometrial polyps: a systematic semi-quantitative review // Eur. J. Gynaecol. Oncol. 2013. Vol. 34. P. 5-22.
24. Kitaya K., Tada Y., Taguchi S., Funabiki M., Hayashi T., Nakamura Y. Local mononuclear cell infiltrates in infertile patients with endometrial macropolyps versus micropolyps // Hum. Reprod. 2012. Vol. 27. P. 3474-3480.
25. Bozkurt M., Sahin L., Ulas M. Hysteroscopic polypectomy decreases NF-kappaB1 expression in the mid-secretory endometrium of women with endometrial polyp // Eur. J. Obstet. Gynecol. Reprod. Biol. 2015. Vol. 189. P. 96-100.
26. Mollo A., Stile A., Alviggi C., Granata M., De Placido G., Perrella A. et al. Endometrial polyps in infertile patients: do high concentrations of interferon-gamma play a role? // Fertil. Steril. 2011. Vol. 96. P. 1209-1212.
27. Zhu Y., Du M., Yi L., Liu Z., Gong G., Tang X. CD4(+) T cell imbalance is associated with recurrent endometrial polyps // Clin. Exp. Pharmacol. Physiol. 2018. Vol. 45. P. 507-513.
28. El-Hamarneh T., Hey-Cunningham A.J., Berbic M., AlJefout M., Fraser I.S., Black K. Cellular immune environment in endometrial polyps // Fertil. Steril. 2013. Vol. 100. P. 1364-1372.
29. Cicinelli E., Bettocchi S., de Ziegler D., Loizzi V., Cormio G., Marinaccio M. et al. Chronic endometritis, a common disease hidden behind endometrial polyps in premenopausal women: first evidence from a case-control study // J. Minim. Invasive Gynecol. 2019. Vol. 26. P. 1346-1350.
30. Sheng K.K., Lyons S.D. To treat or not to treat? An evidence-based practice guide for the management of endometrial polyps // Climacteric. 2020. Vol. 23. P. 336-342. DOI: https://doi.org/10.1080/13697137.2020.1742107
31. American Association of Gynecologic Laparoscopists AAGL practice report: practice guidelines for the diagnosis and management of endometrial polyps // J. Minim. Invasive Gynecol. 2012. Vol. 19. P. 3-10. DOI: https://doi.org/10.1016/j.jmig.2011.09.003
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