High Expression of PR-A and Low Expression of PR-B is Correlated with Inflammation in Endometrioma Cases

Erick Yuane, Agung Dewanto, Shofwal Widad
In: The Indonesian Biomedical Journal · 2023 · vol. 15(1) , pp. 85–93 · doi:10.18585/inabj.v15i1.2114 · W4321479790
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Endometrioma tissues showed higher PR-A and TNF-a expression and lower PR-B and PR-B/A ratio compared to benign cysts, with no significant correlation to endometriosis severity.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 · read from full text ⓘ

This cross-sectional study compared paraffin-embedded tissue samples from 23 ovarian endometriomas and 22 benign ovarian cysts using immunohistochemistry to measure PR-A, PR-B, TNF-α, and the PR-B/A ratio. The authors found that mean PR-B expression and the PR-B/A ratio were lower in endometriomas than in benign cysts, while mean PR-A and TNF-α expression were higher in endometriomas. They reported no significant correlations between PR-A, PR-B, PR-B/A ratio, and TNF-α with endometriosis severity. This paper is centrally about endometriosis — it examines progesterone receptor isoforms and TNF-α distribution in endometrioma versus benign cyst tissues and relates these to inflammation and severity.

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Abstract

BACKGROUND: Progestin therapy has been commonly used in endometriosis. The regulation of progesterone receptors B (PR-B) greatly affects the success rate of therapy in cases of endometriosis. The presence of tumor necrosis factor (TNF)-a in endometriosis triggers PR-B hypermethylation, decreasing PR-B expression and PR-B/A ratio that induce progesterone resistance. It may also occur in endometrioma. Studies regarding the distribution of PR-A and PR-B with TNF-a expression in endometriosis with endometrioma tissue samples has not been elucidated well. Therefore, this study was conducted to measure and compare the distribution of PR-A and PR-B expression, and to assess the effect of PR-B/A ratio on TNF-a in endometrioma and benign cysts.METHODS: A cross-sectional study was conducted by collecting paraffin blocks of endometriomas and benign cysts as controls, from patients undergoing surgery at Dr. Sardjito Hospital, Yogyakarta. Immunohistochemistry was performed to assess the expressions of PR-A, PR-B, TNF-a and PR-B/A ratio, to compared differences between endometriomas and benign cysts.RESULTS: Twenty-three endometrioma and 22 benign cyst tissue samples were collected. The mean PR-B expression and PR-B/A ratio were found to be lower in endometriomas than benign cysts, and mean expression of PR-A and TNF-a in endometriomas was higher than in benign cysts. However, there were no significant correlations between the expression of PR-A, PR-B, PR-B/A ratio, and TNF-a with endometriosis severity.CONCLUSION: In endometrioma cases, the expression of PR-A and TNF-a was higher, while the expression of PR-B and PR-B/A ratio was lower. However, there was no significant relationship between the ratio of PR-B/A and TNF-a.KEYWORDS: progesterone receptor, tumor necrosis factor-alpha, endometriosis, endometrioma, benign cyst, ovarian cyst
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Abstract

BACKGROUND: Progestin therapy has been commonly used in endometriosis. The regulation of progesterone receptors B (PR-B) greatly affects the success rate of therapy in cases of endometriosis. The presence of tumor necrosis factor (TNF)-a in endometriosis triggers PR-B hypermethylation, decreasing PR-B expression and PR-B/A ratio that induce progesterone resistance. It may also occur in endometrioma. Studies regarding the distribution of PR-A and PR-B with TNF-a expression in endometriosis with endometrioma tissue samples has not been elucidated well. Therefore, this study was conducted to measure and compare the distribution of PR-A and PR-B expression, and to assess the effect of PR-B/A ratio on TNF-a in endometrioma and benign cysts.

Methods

A cross-sectional study was conducted by collecting paraffin blocks of endometriomas and benign cysts as controls, from patients undergoing surgery at Dr. Sardjito Hospital, Yogyakarta. Immunohistochemistry was performed to assess the expressions of PR-A, PR-B, TNF-a and PR-B/A ratio, to compared differences between endometriomas and benign cysts.

Results

Twenty-three endometrioma and 22 benign cyst tissue samples were collected. The mean PR-B expression and PR-B/A ratio were found to be lower in endometriomas than benign cysts, and mean expression of PR-A and TNF-a in endometriomas was higher than in benign cysts. However, there were no significant correlations between the expression of PR-A, PR-B, PR-B/A ratio, and TNF-a with endometriosis severity.

Conclusion

In endometrioma cases, the expression of PR-A and TNF-a was higher, while the expression of PR-B and PR-B/A ratio was lower. However, there was no significant relationship between the ratio of PR-B/A and TNF-a.

Keywords

progesterone receptor, tumor necrosis factor-alpha, endometriosis, endometrioma, benign cyst, ovarian cyst Full Text: PDFReferences Falcone T, Flyckt R. Clinical management of endometriosis. Obstet Gynecol. 2018; 131(3): 557–71, CrossRef. Sari V, Jenie RI, Widad S, Dewanto A. MMP-9 and TIMP-1 promote ECM remodeling in the formation of ovarian endometrioma: In vitro study on chicken chorioallantoic membrane. Indones Biomed J. 2022; in press, CrossRef. Saragih CF, Rivany R, Sahil MF, Fadjrir F, Ardiansyah E, Yaznil MR, et al. The difference of Bax protein expression between endometrioma and ovarian carcinoma. Mol Cell Biomed Sci. 2019; 3(2): 95–9, CrossRef. Flores VA, Vanhie A, Dang T, Taylor HS. Progesterone receptor status predicts response to progestin therapy in endometriosis. J Clin Endocrinol Metab. 2018; 103(12): 4561–8, CrossRef. Reis FM, Coutinho LM, Vannuccini S, Batteux F, Chapron C, Petraglia F. Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure. Hum Reprod Update. 2020; 26(4): 565–85, CrossRef. Patel BG, Rudnicki M, Yu J, Shu Y, Taylor RN. Progesterone resistance in endometriosis: origins, consequences and interventions. Acta Obstet Gynecol Scand. 2017; 96(6): 623–32, CrossRef. Attia GR, Zeitoun K, Edwards D, Johns A, Carr BR, Bulun SE. Progesterone receptor isoform A but not B is expressed in endometriosis. J Clin Endocrinol Metab. 2000; 85(8): 2897–902, CrossRef. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012; 98(3): 511–9, CrossRef. Biyik I, Kalkan U, Simsek S. The deep infiltrating endometriosis tissue has lower T-cadherin, E-cadherin, progesterone receptor and oestrogen receptor than endometrioma tissue. Taiwan J Obstet Gynecol. 2021; 60(6): 1059–65, CrossRef. Wu Y, Starzinski-Powitz A, Guo SW. Constitutive and tumor necrosis factor-alpha-stimulated activation of nuclear factor-kappaB in immortalized endometriotic cells and their suppression by trichostatin A. Gynecol Obstet Invest. 2010; 70(1): 23–33, CrossRef. Sun Y, Liu G. Endometriosis-associated ovarian clear cell carcinoma: a special entity? J Cancer. 2021; 12(22): 6773–86, CrossRef. Chae U, Min JY, Kim SH, Ihm HJ, Oh YS, Park SY, et al. Decreased progesterone receptor B/A ratio in endometrial cells by tumor necrosis factor-alpha and peritoneal fluid from patients with endometriosis. Yonsei Med J. 2016; 57(6): 1468–74, CrossRef. Vannuccini S, Clemenza S, Rossi M, Petraglia F. Hormonal treatments for endometriosis: The endocrine background. Rev Endocr Metab Disord. 2022; 23(3): 333–55, CrossRef. Parasar P, Ozcan P, Terry KL. Endometriosis: epidemiology, diagnosis and clinical management. Curr Obstet Gynecol Rep. 2017; 6(1): 34–41, CrossRef. Igarashi TM, Bruner-Tran KL, Yeaman GR, Lessey BA, Edwards DP, Eisenberg E, et al. Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fertil Steril. 2005; 84(1): 67–74, CrossRef. Yong L, Weiyuan Z. Association between body mass index and endometriosis risk: a meta-analysis. Oncotarget. 2017; 8(29): 46928–36, CrossRef. Godinjak Z, Bilalovic N. Estrogen and progesterone receptors in endometrium in women with unexplained infertility. Mater Sociomed. 2014; 26(1): 51–2, CrossRef. Bedaiwy MA, Dahoud W, Skomorovska-Prokvolit Y, Yi L, Liu JH, Falcone T, et al. Abundance and localization of progesterone receptor isoforms in endometrium in women with and without endometriosis and in peritoneal and ovarian endometriotic implants. Reprod Sci. 2015; 22(9): 1153–61, CrossRef. Riccio L da GC, Santulli P, Marcellin L, Abrão MS, Batteux F, Chapron C. Immunology of endometriosis. Best Pract Res Clin Obstet Gynaecol. 2018; 50: 39–49, CrossRef. Nothnick W, Alali Z. Recent advances in the understanding of endometriosis: the role of inflammatory mediators in disease pathogenesis and treatment. F1000Res. 2016; 5: F1000 Faculty Rev-186, CrossRef. Zubrzycka A, Zubrzycki M, Perdas E, Zubrzycka M. Genetic, epigenetic, and steroidogenic modulation mechanisms in endometriosis. J Clin Med. 2020; 9(5): 1309, CrossRef. Copyright (c) 2023 The Prodia Education and Research Institute This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. Indexed by: The Prodia Education and Research Institute

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