Should progesterone and estrogen receptors be assessed for predicting the response to conservative treatment of endometrial hyperplasia and cancer? A systematic review and meta‐analysis

Abstract

Introduction Progestins are used as conservative treatment of endometrial hyperplasia (EH) and early endometrial cancer (EEC). We aimed to assess whether immunohistochemical expression of estrogens and progesterone receptors (ER and PR) predicts the treatment response. Material and methods Electronic databases were searched for studies assessing ER and PR expression in EH and EEC treated with progestins. Relative risk for poor response, sensitivity, specificity, diagnostic odds ratio positive and negative likelihood ratios (LR+ and LR−) and area under the curve (AUC) on summary receiver operating characteristic curve were calculated. Subgroup analyses were based on administration route (oral progestin or levonorgestrel‐intrauterine device) and on histological diagnosis (atypical EH/EEC or non‐atypical EH). Only high accuracy (AUC > 0.9; LR+ >10; LR− <0.1) was considered determining for the clinical practice. Results Thirteen studies with 635 patients were included in the systematic review. Studies at high risk of bias were excluded from the meta‐analysis. Negative ER expression did not significantly predict poor response (P = 0.16), with low predictive accuracy (AUC = 0.637). Negative PR significantly predicted poor response (P = 0.01), with moderate accuracy (AUC = .806). In the oral progestin subgroup, neither ER (P = 0.55) nor PR (P = 0.18) had significant predictive value. In the levonorgestrel‐intrauterine device subgroup, both ER (P < 0.0001) and PR (P = 0.02) were significantly predictive of good response, although the accuracy was suboptimal (LR+ 6.02 and 2.48, respectively; LR− 0.59 and 0.55, respectively). The atypical EH/EEC subgroup showed non‐significant results. Data about non‐atypical EH were not extractable. Conclusions ER and PR expressions are significantly predictive of response in EH and EEC treated with a levonorgestrel‐intrauterine device but not with oral progestins. However, their accuracy is insufficient to be determining in the clinical practice.

Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer

“…Given all these observations, ARID1A evaluation may add important diagnostic and prognostic information in order to adopt a more tailored approach to the patient. Such information may be even more important if we consider the wide range of available treatments for EH ad EC and the inaccuracy of the predictive markers studied . To date, ARID1A appears as the most promising prognostic marker in EH.…”

Hysteroscopy in the management of endometrial hyperplasia and cancer in reproductive aged women: new developments and current perspectives

“…The risk of AEH progressing to EC is related to the presence and severity of cytologic atypia (8,9). Both AEH and EC are the consequence of an increased estrogens concentration, unopposed by progesterone that causes proliferative glandular epithelial changes (10)(11)(12).…”

Immunohistochemical features of benign endometrial hyperplasia in premenopausal women

“…Особливо складною є оцінка фенотипових характеристик ГПЕ у пременопаузальних пацієнток за наявності нестабільного менструального циклу. З урахуванням того, що при ГПЕ можуть мати місце вогнищеві або дифузні ураження з різноманітними цитоархітектурними структурними та клітинними відмінностями, діагностика та прогнозування перебігу ГПЕ залишається складним завданням [1,8,9].…”

“…Particularly difficult is the evaluation of the phenotypic characteristics of EHP in premenopausal women in the presence of an unstable menstrual cycle. Given that EHP can occur as focal or diffuse lesions, with various structural and cytological differences, diagnosis and their prognosis remains a difficult task [1,8,9].…”