Prediction of Relapse After Therapy Withdrawal in Women with Endometrial Hyperplasia: A Long-term Follow-up Study

Sletten, Elise Thoresen; Arnes, Marit; Lyså, Lena Myreng; Moe, Bjørn T.; Straume, Bjørn; Ørbo, Anne

doi:10.21873/anticanres.11595

Cited by 8 publications

(21 citation statements)

References 23 publications

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“…Our present results have demonstrated that low PR‐A in endometrial glands and stroma, and high PR‐B in endometrial glands, in pre‐treatment endometrial biopsies are predictors of relapse after successful progestin therapy for EH. These results are in accordance with a recent publication reporting that low PR‐A in endometrial stroma and high PR‐B in endometrial glands before therapy were correlated with relapse in EH in a retrospective study population . Progesterone receptor levels before therapy were reported only weakly associated with relapse in a study by Gallos et al evaluating expression of estrogen receptor (ER), progesteron receptor (PR), cyclooxygenase subunit 2, Mlh1 and Bcl‐2 as predictors for relapse in women with EH .…”

Section: Discussionsupporting

confidence: 90%

“…These results are in accordance with a recent publication reporting that low PR-A in endometrial stroma and high PR-B in endometrial glands before therapy were correlated with relapse in EH in a retrospective study population. 20 Progesterone receptor levels before therapy were reported only weakly associated with relapse in a study by Gallos et al evaluating expression of estrogen receptor (ER), progesteron receptor (PR), cyclooxygenase subunit 2, Mlh1 and Bcl-2 as predictors for relapse in women with EH. 19 In contrast to our study, the expression of the two isoforms of PR were not separately reported.…”

Section: Main Findingsmentioning

confidence: 99%

“…The individual roles of the PR‐A and PR‐B isoforms in the aetiology and prognosis of EH remain unclear, but a deregulation of PR‐A and PR‐B in either, or both, of the two endometrial tissue compartments (glands and stroma) is likely to be involved in disturbed endometrial proliferation through progression to EH, and EC. However, only a few studies exist that elucidate the prognostic significance of changes in endometrial expression of PR‐A and PR‐B for progestin responsiveness or relapse in EH.…”

Section: Introductionmentioning

confidence: 99%

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

Sletten

Arnes

Lyså

et al. 2019

BJOG

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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.

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Section: Discussionsupporting

confidence: 90%

Section: Main Findingsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Sletten

Arnes

Lyså

et al. 2019

BJOG

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“…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) .…”

Section: Systematic Review Of Biomarkers Of Progestin Responsementioning

confidence: 99%

“…Diabetes has been associated with increased recurrence in one study (128) but not in other studies (127,129,130,137) . Numerous other clinical factors including gravidity (127,129,134) , parity (105,(127)(128)(129)(130)(134)(135)(136)(137) , polycystic ovarian syndrome (105,127,129,131) , smoking (129,133,134) , family history of cancer (127,133) and hypertension (128,130,137) have been investigated in multiple studies, but none has shown an association with outcome.…”

Section: Systematic Review Of Biomarkers Of Progestin Responsementioning

confidence: 99%

Improving response to progestin treatment of low-grade endometrial cancer

Baxter

Brennan

McAlpine

et al. 2020

Int J Gynecol Cancer

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ObjectivesThis review examines how response rates to progestin treatment of low-grade endometrial cancer can be improved. In addition to providing a brief overview of the pathogenesis of low-grade endometrial cancer, we discuss limitations in the current classification of endometrial cancer and how stratification may be refined using molecular markers to reproducibly identify ‘low-risk’ cancers which may represent the best candidates for progestin therapy. We also discuss constraints in current approaches to progestin treatment of low-grade endometrial cancer and perform a systematic review of predictive biomarkers.MethodsPubMed, ClinicalTrials.gov, and Cochrane Library were searched for studies reporting pre-treatment biomarkers associated with outcome in women with low-grade endometrial cancer or endometrial hyperplasia with an intact uterus who received progestin treatment. Studies of fewer than 50 women were excluded. The study protocol was registered in PROSPERO (ID 152374). A descriptive synthesis of pre-treatment predictive biomarkers reported in the included studies was conducted.ResultsOf 1908 records reviewed, 19 studies were included. Clinical features such as age or body mass index cannot predict progestin response. Lesions defined as ‘low-risk’ by FIGO criteria (stage 1A, grade 1) can respond well; however, the reproducibility and prognostic ability of the current histopathological classification system is suboptimal. Molecular markers can be reproducibly assessed, have been validated as prognostic biomarkers, and may inform patient selection for progestin treatment. DNA polymerase epsilon (POLE)-ultramutated tumors and a subset of p53 wild-type or DNA mismatch repair (MMR)-deficient tumors with ‘low-risk’ features (eg, progesterone and estrogen receptor-positive) may have improved response rates, though this needs to be validated.DiscussionMolecular markers can identify cases which may be candidates for progestin treatment. More work is needed to validate these biomarkers and potentially identify new ones. Predictive biomarkers are anticipated to inform future research into progestin treatment of low-grade endometrial cancer and ultimately improve patient outcomes.

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