Morphological and molecular features of recurrent endometrioid ovarian cysts

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

BACKGROUND: One of the clinical course features of ovarian endometriosis is its recurrent nature, which leads to repeated operations and increased damage to the ovarian follicular apparatus.

AIM: The aim of this study was to evaluate morphological and molecular features of recurrent endometrioid ovarian cysts in patients of reproductive age.

MATERIALS AND METHODS: Morphological and immunohistochemical studies of the surgical material of 196 observations of endometrioid ovarian cysts were performed — 23 observations of the first surgical intervention with further diagnosed relapse, 22 observations of repeated surgery and 151 observations of a relapse-free course of endometriosis. Monoclonal mouse antibodies to CD68, transforming growth factor β-1, CD34, and α-smooth muscle actin were used.

RESULTS: CD68 (macrophage) expression was detected in lympho-macrophage infiltrates of the cytogenic stroma and endometrioid cyst capsule. Significantly greater values of the expression were obtained in recurrent endometrioid cysts in the surgical material of both the first (cytogenic stroma — 31 [8; 53]%, capsule — 23 [3; 42]%) and second operation (23 [12; 36] and 9 [5; 20]%, respectively) compared to the relapse-free course of the disease (8 [6; 9] and 2 [0; 4]%, respectively). The transforming growth factor β-1 expression area in the endometrioid cyst capsule was significantly higher in the surgical material of both the first (22.8 [21.6; 24.8]%) and second operation (31.2 [30.5; 32.2]%) with recurrent endometriosis compared to cases with no relapse (12.7 [11.2; 13.9]%). But in the cytogenic stroma was it only detected in cases of repeated surgical endometrioid cyst treatment (18.7 [18.0; 19.7]%). The positive α-smooth muscle actin expression area was higher in the surgical material of the second operation with recurrent endometriosis in both the cytogenic stroma (68.3 [66.3; 69.6]%) and endometrioma capsule (82.5 [80.5; 83.8]%). A large area of CD34 expression was also detected in the recurrent course of ovarian endometriosis in the surgical material of both the first (cytogenic stroma — 34.8 [33.4; 35.8]%, capsule — 52.6 [50.4; 55.0]%) and second operation (51.3 [49.0; 53.3] and 48.7 [46.7; 49.8]%, respectively).

CONCLUSIONS: The recurrent course of ovarian endometriosis is characterized by more pronounced inflammation, angiogenesis, myofibroblast proliferation, and fibrogenesis, which indicates the importance of these pathological processes in the chronicity of the disease. Further study of the role of macrophages and the cascade of regenerative and reparative processes that they trigger is important for understanding the pathogenesis of endometriosis and searching for diagnostic markers of its recurrent course.

Full Text

Restricted Access

About the authors

Nikol N. Petrovskaia

North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: dr.ramzaeva@mail.ru
ORCID iD: 0000-0001-6849-5335
SPIN-code: 7769-1969
Scopus Author ID: 57838172500
Russian Federation, Saint Petersburg

Victoria A. Pechenikova

North-Western State Medical University named after I.I. Mechnikov

Email: p-vikka@mail.ru
ORCID iD: 0000-0001-5322-708X
SPIN-code: 9603-5645

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg

Darya M. Chashchina

North-Western State Medical University named after I.I. Mechnikov

Email: dash.chashina@mail.ru
ORCID iD: 0000-0002-5372-3515
SPIN-code: 1213-8079
Russian Federation, Saint Petersburg

References

  1. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382(13):1244–1256. doi: 10.1056/NEJMra1810764
  2. Fassbender A, Overbergh L, Verdrengh E, et al. How can macroscopically normal peritoneum contribute to the pathogenesis of endometriosis? Fertil. steril. 2011;96(3):697−699. doi: 10.1016/j.fertnstert.2011.06.034
  3. Seo JW, Lee DY, Yoon BK, et al. The age-related recurrence of endometrioma after conservative surgery. Eur J Obstet Gynecol Reprod Biol. 2017;208:81−85. doi: 10.1016/j.ejogrb.2016.11.015
  4. Fedele L, Bianchi S, Zanconato G, et al. Tailoring radicality in demolitive surgery for deeply infiltrating endometriosis. Am J Obstet Gynecol. 2005;193(1):114–117. doi: 10.1016/j.ajog.2004.12.085
  5. Nirgianakis K, Ma L, McKinnon B, et al. Recurrence patterns after surgery in patients with different endometriosis subtypes: a long-term hospital-based cohort study. J Clin Med. 2020;9(2);496. doi: 10.3390/jcm9020496
  6. Moskalev AV, Rudoy AS, Apchel AV, et al. Osobennosti biologii transformirujushhego rostovogo faktora β i immunopatologija. Vestnik Rossijskoj voenno-medicinskoj akademii. 2016;2(54):206–216. (In Russ.)
  7. Symons LK, Miller JE, Kay VR, et al. The immunopathophysiology of endometriosis. Trends in molecular medicine. 2018;24:748–762. doi: 10.1016/j.molmed.2018.07.004
  8. Shigesi N, Kvaskoff M, Kirtley S, et al. The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis. Hum Reprod Update. 2019;25:486–503. doi: 10.1093/humupd/dmz014
  9. Mu F, Harris HR, Rich-Edwards JW, et al. A prospective study of inflammatory markers and risk of endometriosis. Am J Epidemiol. 2018;187(3):515–522. doi: 10.1093/aje/kwx272
  10. Capobianco A, Rovere-Querini P. Endometriosis, a disease of the macrophage. Front Immunol. 2013;4:9. doi: 10.3389/fimmu.2013.00009
  11. Goldmann O, von Köckritz-Blickwede M, Höltje C, et al. E. Transcriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program. Infect Immun. 2007;75(8):4148–4157. doi: 10.1128/IAI.00181-07
  12. Martinez FO, Sica A, Mantovani A, et al. Macrophage activation and polarization. Front Biosci. 2008;13:453–461. doi: 10.2741/2692
  13. Bacci M, Capobianco A, Monno A, et al. Macrophages are alternatively activated in patients with endometriosis and required for growth and vascularization of lesions in a mouse model of disease. Amn J Pathol. 2009;175(2):547–556. doi: 10.2353/ajpath.2009.081011
  14. Smith KA, Pearson CB, Hachey AM, et al. Alternative activation of macrophages in rhesus macaques (Macaca mulatta) with endometriosis. Comp Med. 2012;62(4):303–310.
  15. Hu W, Li X, Zhang C, et al. Tumor-associated macrophages in cancers. Clin Transl Oncol. 2016;18(3):251–258. doi: 10.1007/s12094-015-1373-0
  16. Kuz’mina N.S. Novyye podkhody k preodoleniyu besplodiya u bol’nykh s endometriomami yaichnikov pri snizhenii ovarial’nogo rezerva [dissertation abstract]. Saint Petersburg; 2019. [cited 2022 Sept 15]. Available from: https://www.dissercat.com/content/novye-podkhody-k-preodoleniyu-besplodiya-u-bolnykh-s-endometriomami-yaichnikov-pri-snizhenii
  17. Velikorodnaya YuI, Pocheptsov AYa. Dynamic changes in vimetin and smooth muscle actin ratio in experimental chemically induced liver fibrosis. Vestnik VolgGMU. 2014;3(51):55−58. (In Russ.)
  18. Ellinidi VN, Kuzmina NS, Simonova IE, et al. Novye vozmozhnosti primeneniya α-SMA-biomarkera rannei stadii fidroza pri khronicheskom endometrite u bol’nykh endo-metriozom. Obstetrics and Gynaecology of St. Petersburg. 2018;(3–4):65−69. (In Russ.)
  19. Hinz B. Myofibroblasts. Exp Eye Res. 2016;142:56–70. doi: 10.1016/j.exer.2015.07.009
  20. Adamyan LV, Aznaurova YaB. Molecular aspects of endometriosis. Problemy Reproduktsii. 2015;21(2):66-77. (In Russ.). doi: 10.17116/repro201521266-77
  21. Choi HJ, Park MJ, Kim BS, et al. Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression. BMB Rep. 2017;50(8):429–434. doi: 10.5483/bmbrep.2017.50.8.097
  22. Florova MS. The role of growth factors in the pathogenesis of endometriosis. Journal of Obstetrics and Women’s Diseases. 2019;68(3):71–80. doi: 10.17816/JOWD68371-80

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Myofibroblast-like cell proliferation in the cytogenic stroma of the endometrioid ovarian cyst. Hematoxylin-eosin stain; a, survey image, zoom ×100; b, fragment, zoom ×200

Download (291KB)
Indexing metadata
3. Fig. 2. CD68 expression data in the endometrial cytogenic stroma and endometrioid cyst capsule: 1, first operation followed by relapse; 2, second operation (for relapse); 3, relapse-free course of endometriosis

Download (289KB)
Indexing metadata
4. Fig. 3. CD68 expression in ovarian endometriosis: a, cytogenic stroma, relapse, first operation; b, cyst capsule, relapse, first operation; c, cytogenic stroma, relapse, second operation; d, cyst capsule, relapse, second operation; e, cytogenic stroma, relapse-free course; f, cyst capsule, relapse-free course. Immunohistochemistry study, zoom ×200

Download (318KB)
Indexing metadata
5. Fig. 4. Transforming growth factor β-1 expression in endometrioid ovarian cysts: a, cyst capsule, relapse, first operation; b, cyst capsule, relapse, second operation; c, cyst capsule, no relapse; d, cytogenic stroma, relapse, second operation. Immunohistochemistry study, zoom ×200

Download (284KB)
Indexing metadata
6. Fig. 5. α-Smooth muscle actin expression in ovarian endometriosis: a, cytogenic stroma, relapse, first operation; b, cyst capsule, relapse, first operation; c, cytogenic stroma, relapse, second operation; d, cyst capsule, relapse, second operation; e, cytogenic stroma, no relapse; f, cyst capsule, no relapse. Immunohistochemistry study, zoom ×200

Download (533KB)
Indexing metadata
7. Fig. 6. CD34 expression in ovarian endometriosis: a, cytogenic stroma, relapse, first operation; b, cyst capsule, relapse, first operation; c, cytogenic stroma, relapse, second operation; d, cyst capsule, relapse, second operation; e, cytogenic stroma, no relapse; f, cyst capsule, no relapse. Immunohistochemistry study, zoom ×100

Download (404KB)
Indexing metadata

Copyright (c) 2022 Eсо-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 66759 от 08.08.2016 г. 
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия Эл № 77 - 6389 от 15.07.2002 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies