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

BJOG. 2019 Jun;126(7):936-943. doi: 10.1111/1471-0528.15579. Epub 2019 Jan 25.

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.

Keywords: Endometrial hyperplasia; progesterone receptor; progestin; relapse.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Endometrial Hyperplasia / complications*
  • Endometrial Hyperplasia / drug therapy*
  • Female
  • Humans
  • Middle Aged
  • Progestins / therapeutic use
  • Receptors, Progesterone / metabolism*
  • Recurrence
  • Retrospective Studies

Substances

  • Biomarkers
  • Progestins
  • Receptors, Progesterone
  • progesterone receptor A
  • progesterone receptor B