分子分型预测子宫内膜癌及子宫内膜非典型增生患者保留生育功能治疗后的预后及生育结局

Molecular classification predicts prognosis and fertility outcomes after fertility-preserving treatment for endometrial cancer and atypical endometrial hyperplasia

目的:分析不同分子分型对接受保留生育功能治疗的子宫内膜癌(EC)及子宫内膜非典型增生(AEH)患者肿瘤预后及妊娠结局的影响。方法:回顾性收集2012年1月至2021年12月在郑州大学第一附属医院接受保留生育功能治疗的95例EC或AEH患者的临床资料。采用Sanger测序和免疫组化染色(IHC)方法,根据EC前瞻性分子危险分类法(ProMisE)将患者分为4组:POLE核酸外切酶域突变型(POLE EDM)、错配修复缺陷型(MMRd)、p53突变型(p53abn)和p53野生型(p53wt)。比较分析不同分子分型患者的一般情况、肿瘤预后及生育结局。结果:对95例患者首次就诊时的病理组织进行检测,其中POLE EDM型2例、MMRd型25例、p53abn型5例、p53wt型63例。MMRd型和p53wt型的一般情况、肿瘤预后及生育结局比较,差异无统计学意义(P>0.05)。根据病变严重程度进行亚组分析,EC亚组中MMRd型和p53wt型患者的复发率分别为66.7%和16.7%(P=0.019),AEH亚组中MMRd和p53wt组患者的妊娠率分别为18.2%和71.4%(P=0.006),差异均有统计学意义。根据不同的治疗方法,接受口服高效孕激素治疗的MMRd型和p53wt型患者在9个月时的完全缓解率分别为50.0%和82.9%,差异有统计学意义(P=0.046)。结论:分子分型对早期EC及AEH患者接受保留生育功能治疗前进行评估是可行的。MMRd型和p53wt型在接受保留生育治疗后均表现出良好的预后和生育结果,其中p53wt型可能获益更多。

Objective:To explore the impact of molecular classification on tumor prognosis and fertility outcomes among patients with endometrial carcinoma(EC)and atypical endometrial hyperplasia(AEH)who underwent fertility-preserving therapy.Methods:This study retrospectively collected clinical data on 95 patients with EC or AEH who received fertility-preserving treatment at the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2021.Immunohistochemistry(IHC)and Sanger sequencing were used to divide the patients into four subtypes based on proactive molecular risk classifier for endometrial cancer(ProMisE):POLE exonuclease domain mutation(POLE EDM),mismatch repair deficient(MMRd),p53 abnormal(p53abn),p53 wild type(p53wt).The general characteristics,tumor prognosis,and fertility outcomes between different molecular subgroups were analyzed and compared.Results:A total of 95 patients'pathological tissues at the first visit were examined,of which 2 were of POLE EDM subtype,25 of MMRd subtype,5 of p53abn subtype,and 63 of p53wt subtype.There was no statistically significant difference between MMRd type and p53wt type in general conditions,tumor prognosis,and fertility outcomes(P>0.05).Subgroup analysis based on disease severity revealed that recurrence rates in the EC subgroup were 66.7%for MMRd patients and 16.7%for p53wt patients(P=0.019).In the AEH subgroup,pregnancy rates were 18.2%for MMRd patients and 71.4%for p53wt patients(P=0.006),showing statistically significant differences.When considering different treatment methods,complete response rates after 9 months of oral high-potency progesterone treatment were 50.0%for MMRd patients and 82.9%for p53wt patients,with a statistically significant difference(P=0.046).Conclusion:Molecular classification is feasible for the evaluation of patients with early EC and AEH prior to fertility-preserving treatment.Both MMRd and p53wt subtypes demonstrate favorable prognosis and fertility outcomes following fertility-sparing treatment,with p53wt subtype possibly providing greater benefit.