Shao W Y, Dong Y T, Lyu Q Y, Liao J B, Xue Y, Chen X J
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200092, China.
Clinical Medical College, Fudan University, Shanghai 200032, China.
Zhonghua Fu Chan Ke Za Zhi. 2023 Oct 25;58(10):742-754. doi: 10.3760/cma.j.cn112141-20230719-00011.
To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; =0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; =0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (=0.413, 95%: 0.259-0.658; <0.001) and PIK3CA gene mutation (=0.499, 95%: 0.310-0.804; =0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (=3.825, 95%: 1.570-9.317; =0.003) and MMR-d (=9.014, 95%: 1.734-46.873; =0.009) were independent risk factors of recurrence in EC and AEH patients. No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.
探讨分子分类和关键致癌基因对接受保留生育功能治疗的子宫内膜癌（EC）和非典型子宫内膜增生（AEH）患者肿瘤学结局的影响。回顾了2021年1月至2023年3月在复旦大学附属妇产科医院接受基于孕激素的保留生育功能治疗并进行分子分类以及关键致癌基因检测的EC和AEH患者。在开始激素治疗前以及治疗期间每3个月进行宫腔镜下病变切除和子宫内膜活检以评估疗效。进一步分析影响EC和AEH患者治疗结局的危险因素。在分析的171例患者中，中位年龄为32岁，其中EC患者86例，AEH患者85例。分子分类分布如下：157例（91.8%）分类为无特定分子特征（NSMP）；9例（5.3%）为错配修复缺陷（MMR-d）；3例（1.8%）为POLE突变；2例（1.2%）为p53异常。NSMP或MMR-d患者的累积40周完全缓解（CR）率无差异（61.6%对60.0%；P=0.593），而MMR-d患者CR后复发风险高于NSMP患者（50.0%对14.4%；P=0.005）。多变量分析显示PTEN基因多位点突变（P=0.413，95%CI：0.259-0.658；P<0.001）和PIK3CA基因突变（P=0.499，95%CI：0.310-0.804；P=0.004）与较低的累积40周CR率相关，孕激素不敏感（P=3.825，95%CI：1.570-9.317；P=0.003）和MMR-d（P=9.014，95%CI：1.734-46.
