Significance of progesterone receptors (PR‐A and PR‐B) expression as predictors for relapse after successful therapy of endometrial hyperplasia: a retrospective cohort study

Abstract

Objective After successful progestin therapy for endometrial hyperplasia (EH), the risk of relapse remains. We aimed to assess if immunohistochemical (IHC) expression of progesterone receptor isoforms, PR‐A and PR‐B, in endometrial glands and stroma in pre‐treatment endometrial biopsies was related to relapse of EH. Design and setting Biopsy material originated from women with low‐risk and medium‐risk EH recruited to a recent Norwegian multicentre randomised trial. Participants (n = 153) had been treated for 6 months with three different progestin regimens. Population One hundred and thirty‐five of the 153 women achieved therapy response and underwent follow up for 24 months after therapy withdrawal. Fifty‐five women relapsed during follow up. Pre‐treatment endometrial biopsies from 94 of the 135 responding women were available for IHC staining. Methods Immunohistochemical staining was performed separately for PR‐A and PR‐B and IHC expression was evaluated in endometrial glands and stroma by a histological score (H‐score) using light microscopy. Main outcome measure Immunohistochemical expression of PR‐A and PR‐B in endometrial glands and stroma in women with or without relapse of EH. Results Low PR‐A in endometrial glands (P = 0.013) and stroma (P < 0.001), and high PR‐B in endometrial glands (P = 0.001) in pre‐treatment endometrial biopsy have a statistically significant association with relapse of EH. Women with a pre‐treatment ratio of PR‐A:PR‐B ≤ 1 have a higher risk of relapse (71%) compared with women with a ratio of PR‐A:PR‐B > 1 (19%; P < 0.001). Conclusion Immunohistochemical expression of PR‐A and PR‐B in pre‐treatment endometrial biopsy proves valuable as a predictor of relapse in EH. Tweetable abstract Pre‐treatment endometrial expression of PR‐A and PR‐B is a valuable predictor of relapse in endometrial hyperplasia.

Improving response to progestin treatment of low-grade endometrial cancer

“…Many studies investigating BMI reported that obesity was associated with failure to achieve disease regression and increased recurrence (105,(127)(128)(129)(130) . However, a recent study of Japanese women reported that lower BMI was associated with increased recurrence (131) , whilst numerous studies have reported no association between BMI and outcome (132)(133)(134)(135)(136)(137) . The association between age or menopause status and outcome are also conflicting, with two studies reporting younger age or premenopausal status were associated with disease regression or reduced recurrence (127,132) , whilst another reported younger age was associated with increased recurrence (136) .…”

Current Knowledge on Endometriosis Etiology: A Systematic Review of Literature

“…Here, a normal endometrium is composed of stromal cells which express an abundant amount of the PR and results in a paracrine effect in epithelium proliferation and differentiation. 90 , 91 Even though stroma decidualization is the main result of the actions of progesterone, the most pronounced difference between PR expression in infertile females and fertile controls occurs in epithelial cells. 92 …”

“…Here, a normal endometrium is composed of stromal cells which express an abundant amount of the PR and results in a paracrine effect in epithelium proliferation and differentiation. 90,91 Even though stroma decidualization is the main result of the actions of progesterone, the most pronounced difference between PR expression in infertile females and fertile controls occurs in epithelial cells. 92 While most studies suggest a characteristic change in the receptor expression of steroid hormones in the eutopic endometrium (endometriosis), a study from the Sao-Paulo University (Brazil) showed no significant differences in PR expression compared to the control group.…”

Involvement of the Estrogen and Progesterone Axis in Cancer Stemness: Elucidating Molecular Mechanisms and Clinical Significance

“…It is easy to differentiate between PR-A and PR-B using western blotting because their molecular weights markedly differ. Immunohistochemistry (IHC) can also be used to identify them in clinical biopsy specimens ( 151 ), but antibodies used for the detection of PR-A have been found to detect not only PR-A but also PR-B ( 152 ). Thus, developing new antibodies to distinguish one isoform from the other is pivotal for predicting tumor malignancy and for the clinical prognosis of patients.…”