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Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage
Published on: August 4, 2021
Immunocytochemical markerprofile of endometriotic epithelial, endometrial epithelial, and mesothelial cells: a
R F Kruitwagen1, L G Poels, W N Willemsen
1Department of Obstetrics and Gynecology, School of Medicine, University of Nijmegen, The Netherlands.
Insights
Immunocytochemistry distinguished endometriotic cells from mesothelial cells using specific markers, supporting the endometrial implantation theory for endometriosis. However, mesothelial metaplasia cannot be entirely ruled out.
Area of Science:
- Gynecologic pathology
- Cell biology
- Immunohistochemistry
Background:
- Endometriosis, a condition involving endometrial-like tissue outside the uterus, has two main proposed origins: endometrial implantation or mesothelial metaplasia.
- Distinguishing between these origins is crucial for understanding endometriosis pathogenesis.
Purpose of the Study:
- To investigate the cellular origins of endometriosis by comparing endometriotic epithelial cells with endometrial epithelial and mesothelial cells using immunocytochemistry.
- To identify specific markers that can differentiate these cell types.
Main Methods:
- Comparative immunocytochemical analysis of endometriotic, endometrial, and mesothelial cells.
- Utilized monoclonal antibodies (MAbs) against keratins, epithelial markers (HMFG-2, BW 495/36), a novel endometrial-specific MAb (NEND-3), and ovarian carcinoma-related antigens.
- Confirmed findings on both frozen sections and cultured cells.
Main Results:
- Keratin subtyping did not differentiate the cell types.
- Epithelial markers HMFG-2, BW 495/36, and particularly NEND-3, successfully distinguished endometrial/endometriotic cells from mesothelial cells.
- NEND-3 showed specificity for endometrial and endometriotic epithelial cells.
- Ovarian carcinoma antigen markers provided insufficient distinction.
Conclusions:
- The findings support the endometrial implantation theory of endometriosis.
- However, the possibility of mesothelial metaplasia cannot be excluded, as metaplastic mesothelium may exhibit altered antigen expression.
Abstract:
A comparative immunocytochemical study was performed on endometriotic epithelial versus endometrial epithelial and normal mesothelial cells in order to obtain further evidence for either the endometrial implantation or mesothelial metaplasia theory. The three cell types could not be distinguished by keratin subtyping, using monoclonal antibodies (MAbs) to keratins 5, 7, 8, 14, 18, and 19. The epithelial markers HMFG-2 and BW 495/36, and a newly developed MAb NEND-3 (against endometrial cells) discriminated between generally negatively reacting mesothelial cells and positively reacting endometrial and endometriotic epithelial cells. The MAb NEND-3 appeared to be specific for endometrial (and endometriotic) epithelial cells since no reactivity with other epithelial cell types was found. Typing with MAbs against ovarian carcinoma related antigens (OV-TL 3, OV-TL 10 and OC 125) did not permit sufficient distinction. The marker profile of cultured endometrial, endometriotic and mesothelial cells confirmed the immunocytochemical findings on frozen sections. Although the data are consistent with the endometrial implantation theory, mesothelial metaplasia can not be excluded with regard to the histogenesis of endometriosis since metaplastic mesothelium may express different antigen markers.
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