Obstetrics and Gynecology Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.
Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy.
Acta Obstet Gynecol Scand. 2019 Aug;98(8):976-987. doi: 10.1111/aogs.13586. Epub 2019 Mar 28.
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.
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.
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.
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.
孕激素被用作子宫内膜增生（EH）和早期子宫内膜癌（EEC）的保守治疗方法。我们旨在评估雌激素和孕激素受体（ER 和 PR）的免疫组织化学表达是否可预测治疗反应。
电子数据库中搜索了评估接受孕激素治疗的 EH 和 EEC 中 ER 和 PR 表达的研究。计算不良反应的相对风险、敏感性、特异性、诊断优势比阳性和阴性似然比（LR 和 LR ）以及汇总受试者工作特征曲线下的面积（AUC）。基于给药途径（口服孕激素或左炔诺孕酮宫内节育器）和组织学诊断（非典型 EH/EEC 或非典型 EH）进行亚组分析。仅考虑高准确性（AUC>0.9；LR>10；LR<0.1）对临床实践有决定性。
系统评价共纳入 13 项研究，涉及 635 例患者。排除了存在高偏倚风险的研究后进行了荟萃分析。阴性 ER 表达并未显著预测不良反应（P=0.16），预测准确性较低（AUC=0.637）。阴性 PR 显著预测不良反应（P=0.01），具有中等准确性（AUC=0.806）。在口服孕激素亚组中，ER（P=0.55）或 PR（P=0.18）均无显著预测价值。在左炔诺孕酮宫内节育器亚组中，ER（P<0.0001）和 PR（P=0.02）均对良好反应有显著预测作用，尽管准确性欠佳（LR 分别为 6.02 和 2.48；LR 分别为 0.59 和 0.55）。非典型 EH/EEC 亚组结果无统计学意义。无法提取关于非典型 EH 的数据。
在接受左炔诺孕酮宫内节育器治疗的 EH 和 EEC 中，ER 和 PR 表达与治疗反应显著相关，但在接受口服孕激素治疗的患者中则无相关性。然而，其准确性还不足以在临床实践中具有决定性。
