Prostaglandin E2 receptor EP1 in healthy and diseased human endometrium

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This study assessed prostaglandin E2 receptor EP1 staining intensity in healthy and pathological endometrium, finding cyclical changes in healthy tissue and increased epithelial EP1 in endometriosis and differences in stromal EP1 in cancer.

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This retrospective immunohistochemistry study examined prostaglandin E2 receptor EP1 staining intensity in human nonpregnant endometrium across the menstrual cycle and compared EP1 expression in healthy endometrium versus ovarian endometriosis and endometrial cancer. EP1 showed cyclical changes with increased staining in both endometrial epithelium and stroma during the proliferative phase, and epithelium EP1 staining was higher in endometriotic tissue than in healthy endometrium and tumor tissue. In contrast, stromal EP1 staining was lower in tumor than in both normal tissue and endometriosis, and no significant associations were found with endometrial cancer histology, stage, grade, metastasis, recurrence, or with progression-free or overall survival; stronger EP1 staining was observed in progesterone receptor B–positive tumors versus PRB-negative tumors. This paper is centrally about endometriosis — it directly compares EP1 staining between healthy endometrium and ovarian endometriosis tissue and reports epithelium EP1 upregulation in endometriosis.

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Abstract

Prostaglandin E2 (PGE2) is well described to be associated with both endometrial functions and disorders. The primary aim of this study was to explore the underlying mechanisms that affect the growth and function of endometrial epithelium and stroma by assessing the staining intensity of PGE2 receptors (EP) in healthy endometrium across the menstrual cycle and in pathological endometrium, such as ovarian endometriosis and endometrial cancer. We retrospectively analyzed the EPs staining intensity in human nonpregnant endometrium throughout the menstrual cycle by immunohistochemistry and further focused on EP1 (n = 42). The variation of EP1 was compared among healthy endometrium, ovarian endometriosis (n = 14), and endometrial cancer (n = 140) crosswise. EP1 presented cyclical changes with increased intensity in both epithelium and stroma during the proliferative phase. EP1 staining in the epithelium was increased in endometriotic tissue compared to healthy endometrium and tumor tissue, while in the stroma, the staining in the tumor was lower than that in both normal tissue and endometriosis. No significant differences in EP1 intensity were detected for histological, stage, grading, metastatic and recurrent subtypes in endometrial cancer. EP1 was also correlated with neither progression-free survival nor overall survival of patients with cancer. EP1 staining in progesterone receptor B (PRB)-positive tumor was stronger compared to PRB-negative tumor. EP1 may play a role in human endometrial physiology and pathology. Further studies on the effect of EP1 on human endometrium are needed. Similar content being viewed by others

References

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Acknowledgements

We thank China Scholarship Council for awarding Junyan Zhu a scholarship. The sponsors did not participate in study design, data analysis, and writing the manuscript. We gratefully acknowledge the help of Eileen Deuster for correcting sentence structure and grammar. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest All authors declare no conflict of interest. Electronic supplementary material Below is the link to the electronic supplementary material. 418_2017_1616_MOESM1_ESM.tif (download TIF ) Supplementary material 1 Representative microphotographs of positive (A) and negative controls (B) for EP1 in placenta tissue are shown. Scale bars equal 100 μm (TIFF 2966 kb) Rights and permissions About this article Cite this article Zhu, J., Mayr, D., Kuhn, C. et al. Prostaglandin E2 receptor EP1 in healthy and diseased human endometrium. Histochem Cell Biol 149, 153–160 (2018). https://doi.org/10.1007/s00418-017-1616-y Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00418-017-1616-y

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MeSH descriptors

Endometrial Neoplasms Endometrium Receptors, Prostaglandin E, EP1 Subtype Adult Aged Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Endometrium Endometrium Endometrium Female Humans Middle Aged Receptors, Prostaglandin E, EP1 Subtype Receptors, Prostaglandin E, EP1 Subtype

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