Objective: 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. Methods: 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. Results: 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%; P=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%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: 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.
目的： 探讨分子分型及关键致癌基因突变对子宫内膜癌（EC）和子宫内膜非典型增生（AEH）患者保留生育功能治疗结局的影响。 方法： 收集2021年1月至2023年3月在复旦大学附属妇产科医院接受高效孕激素保留生育功能治疗并进行分子分型及关键致癌基因检测的171例EC和AEH患者进行回顾性分析；所有患者在开始孕激素治疗前及治疗后约每3个月进行1次宫腔镜病灶切除及子宫内膜活检病理检查，用于评估疗效；进一步对影响EC和AEH患者治疗结局的相关因素进行分析。 结果： 171例EC和AEH患者的中位年龄为32岁；EC 86例，AEH 85例；分子分型：无特殊分子改变（NSMP）型157例（91.8%），错配修复缺陷（MMR-d）型9例（5.3%），POLE突变型3例（1.8%），p53异常型2例（1.2%）。NSMP型与MMR-d型患者治疗40周累积完全缓解（CR）率比较，差异无统计学意义（分别为61.6%、60.0%；P=0.593）；但与NSMP型患者相比，MMR-d型患者CR后的1年累积复发率显著升高（分别为14.4%、50.0%；P=0.015）。多因素分析显示，子宫内膜病变组织中存在PTEN基因多个位点突变（HR=0.413，95%CI为0.259~0.658；P<0.001）、PIK3CA基因突变（HR=0.499，95%CI为0.310~0.804；P=0.004）均为影响40周累积CR率的独立危险因素，难治性（HR=3.825，95%CI为1.570~9.317；P=0.003）和MMR-d型（HR=9.014，95%CI为1.734~46.873；P=0.009）均为影响EC和AEH患者复发的独立危险因素。 结论： 在采用高效孕激素保留生育功能治疗的EC和AEH患者中，分子分型为NSMP型与MMR-d型患者的40周累积CR率比较无显著差异，可能与患者均接受宫腔镜评估有关；但MMR-d型患者CR后的复发风险更高。PTEN或PIK3CA基因突变可能与子宫内膜病变组织更低的孕激素反应有关。分子特征有助于预测EC和AEH患者孕激素保留生育功能治疗的疗效。.