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

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.