Immunohistochemical features of endometrial stem cells: morphological aspects

Authors

DOI:

https://doi.org/10.26641/1997-9665.2024.3.13-19

Keywords:

pathomorphology, immunohistochemistry, endometrial hyperplasia, basal endometrium, stem cells.

Abstract

Introduction. Menstruation is a unique biological phenomenon that occurs in a limited number of mammals such as humans and other higher primates. The endometrium changes dramatically depending on the phases of the menstrual cycle (ie, proliferative phase, secretory phase, and menstruation) and plays a critical role in the implantation of fertilized eggs. Purpose. To study the morphological and immunohistochemical features of endometrial stem cells with the study of the expression of ER, PgR, Ki67, CK PAN, PAX2, PAX8, PTEN markers that may have an impact on the development of endometrial hyperplasia. Methods. The work examines endometrial material obtained by diagnostic biopsy from 21 women with abnormal uterine bleeding (ABM). Primary monoclonal antibodies ER, PgR, CK PAN, Ki-67, PAX2, PAX8, PTEN and the UltraVision Quanto imaging system (LabVision) were used for IHC studies. Results. The endometrial glands of the deepest part of the basal layer during the menstrual cycle only weakly respond to estrogen stimulation and are completely insensitive to progesterone, which is very clearly visible in the control group (on the secretory endometrium) during an immunohistochemical study (IGH) with markers for estrogen and progesterone receptors. But the phenomenon of division of progenitor cells/stem cells can most clearly be traced to the phase of active proliferation, which also persists during hyperplastic processes in the endometrium. The expression of such specific markers as PAX2, PAX8, PTEN, of the control group was also detected in the basal layer of the hyperplastic endometrium, which confirms the homogeneity of the progenitor/stem cell phenotypes of the stroma and parenchyma. Conclusion. In the basal and functional layers of the endometrium, the difference in the expression of ER and PgR in the stroma and epithelial cells indicates a different way of activating the proliferation of reserve cells that may be involved in the processes of hyperplasia formation. The fact that the stroma actively responds to the hormonal signal of estrogen, while epithelial cells do not show sensitivity to estrogen, and the fact that the majority of stromal cells have a higher level of proliferation than the epithelium of the glands indicates a significant contribution of the influence of the stromal component to the formation of hyperplastic processes of the endometrium. The functional zone is a layer of the endometrium that undergoes cyclical changes depending on a woman's menstrual bleeding. There is a regular renewal of cells that express CK PAN, PAX2, PAX8, PTEN, which remain typical markers of epithelial cells of the endometrium. The basal layer of the endometrium responds poorly to estrogen stimulation and is almost insensitive to progesterone, but continues to express CK PAN, PAX2, PAX8, PTEN, along with reserve cells.

References

  1. Sanderson PA, Critchley HO, Williams AR, Arends MJ, Saunders PT. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Human reproduction update. 2017;23(2):232-254. https://doi.org/10.1093/humupd/dmw042
  2. Chandra V, Kim JJ, Benbrook DM, Dwivedi A, Rai RJ. Therapeutic options for management of endometrial hyperplasia. Gynecol Oncol. 2016;27(1):88-98. doi: 10.3802/jgo.2016.27.e8
  3. Padykula HA, Coles LG, Okulicz WC, Rapaport SI, McCracken JA, King NW Jr, Longcope C, Kaiserman-Abramof IR. The basalis of the primate endometrium: a bifunctionalgerminal compartment. Biology of Reproduction. 1989;40:681-690.
  4. Shevra CR, Ghosh A, Kumar M. Cyclin D1 and Ki-67 expression in normal, hyperplastic and neoplastic endometrium. Journal of postgraduate medicine. 2015;61(1):15-20. https://doi.org/10.4103/ 0022-3859.147025
  5. Yang YF, Liao YY, Peng NF, Li LQ, Xie SR, Wang RB. Prediction of coexistent carcinomas risks by subjective EIN diagnosis and comparison with WHO classification in endometrial hyperplasias. Pathol Res Pract. 2012;208(12):708-712. doi: 10.1016/j.prp.2012.08.009
  6. Kim JJ, Chapman-Davis E. Role of progesterone in endometrial cancer. Semin. Reprod. Med. 2010;28:81-90. doi: 10.1055/s-0029-1242998
  7. Vareniuk IM, Dzerzhynskyi ME, authors. [Methods of cyto-histological diagnosis: study guide]. Kyiv. 2019. 256 p. Ukrainian.
  8. Nguyen T, author. Immunohistochemistry: A Technical Guide to Current Practices. Cambridge: Cambridge University Press; 2022. 272 p.
  9. Antunes A, Vassallo J, Pinheiro A, Leao R, Pinto Neto AM, Costa-Paiva L. Immunohistochemical expression of estrogen and progesterone receptors in endometrial polyps: A comparison between benign and malignant polyps in postmenopausal patients. Oncol Lett. 2014;7(6):1944-1950. doi: 10.3892/ol.2014.2004
  10. Peiró G, Diebold J, Baretton GB, Kimmig R, Löhrs U. Cellular apoptosis susceptibility gene expression in endometrial carcinoma: correlation with Bcl-2, Bax, and caspase-3 expression and outcome. Int J Gynecol Pathol. 2001;20(4):359-367. doi: 10.1097/00004347-200110000-00008
  11. Cousins FL, Pandoy R, Jin S, Gargett CE. The Elusive Endometrial Epithelial Stem/Progenitor Cells. Frontiers in Cell and Developmental Biology. 2021;9:640319. https://doi.org/10.3389/fcell.2021.640319
  12. Yamaguchi M, Yoshihara K, Suda K, Nakaoka H, Yachida N, Ueda H, Sugino K, Mori Y, Yamawaki K, Tamura R, Ishiguro N, Motoyama T, Watanabe Y, Okuda Y, Tainaka K, Enomoto T. Three-dimensional understanding of the morphological complexity of the human uterine endometrium. iScience. 2021;24:102258. doi.org/10.1016/j.isci.2021.102258

Published

2024-10-30

How to Cite

Poslavska , O., Shponka , I., Khaskhachikh , D., & Potapov , V. (2024). Immunohistochemical features of endometrial stem cells: morphological aspects. Морфологія / Morphologia / Morfologìâ, 18(3), 13–19. https://doi.org/10.26641/1997-9665.2024.3.13-19

Issue

Section

Статті