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保留生育功能治疗后子宫内膜癌患者的分子分类:ProMisE分类器的应用及预后证据的组合

Molecular Classification in Patients With Endometrial Cancer After Fertility-Preserving Treatment: Application of ProMisE Classifier and Combination of Prognostic Evidence.

作者信息

Ran Xuting, Hu Tingwenyi, Li Zhengyu

机构信息

Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China.

Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.

出版信息

Front Oncol. 2022 May 19;12:810631. doi: 10.3389/fonc.2022.810631. eCollection 2022.

DOI:10.3389/fonc.2022.810631
PMID:35664732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9160735/
Abstract

The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) is a molecular classification system that identifies endometrial cancer (EC) into four prognostically distinct subtypes: -mutated, mismatch repair deficiency (MMR-D), p53 wild-type (p53wt), and p53 abnormal (p53abn). However, few reports have applied the ProMisE classifier to EC patients who underwent fertility-preserving treatment (FPT) so far. This study evaluated whether the ProMisE classifier predicted in early-stage EC patients after FPT. We first summarized the three reported outcomes of ProMisE applied to EC patients who received FPT. The hormone-treated patients with EC from 2010 to 2020 in our facility were then analyzed. By sequential immunohistochemistry and Sanger sequencing of according to the ProMisE system, formalin-fixed paraffin-embedded blocks of patients before treatment were collected and classified into -mutated, MMR-D, p53wt, and p53abn subtypes. The primary outcome was a complete response rate after FPT. Thirteen patients were enrolled from our facility, with 3 (3/13) MMR-D, 0 (0/13) POLE, 8 (8/13) p53wt, 1 (1/13) p53abn, and 1 (1/13) failed with DNA amplification. Six (6/8) patients with p53wt, 2 (2/3) patients with MMR-D, and 1 (1/1) patient with p53abn achieved a complete response in 6 months after treatment. The results of our study and the reported outcomes were finally combined. A total of 106 patients who underwent FPT were included. Of these, 23 (21.7%) were classified as MMR-D, 3 (2.8%) as -mutated, 3 (2.8%) as p53abn, and 77 (72.6%) as p53wt. There was no significant difference in the complete response rate (P = 0.152) and recurrence rate (P = 0.174) between MMR-D and p53wt subtypes after FPT. Based on current data, we observed no prognostic significance of the ProMisE classifier in EC patients who underwent FPT. Larger prospective studies are needed to elucidate the precise prognostic meaning of this molecular classifier in these cases.

摘要

子宫内膜癌前瞻性分子风险分类器(ProMisE)是一种分子分类系统,可将子宫内膜癌(EC)分为四种预后不同的亚型:POLE突变型、错配修复缺陷型(MMR-D)、p53野生型(p53wt)和p53异常型(p53abn)。然而,迄今为止,很少有报告将ProMisE分类器应用于接受保留生育功能治疗(FPT)的EC患者。本研究评估了ProMisE分类器是否能预测FPT后早期EC患者的情况。我们首先总结了已报道的将ProMisE应用于接受FPT的EC患者的三项结果。然后对2010年至2020年在我们机构接受激素治疗的EC患者进行了分析。根据ProMisE系统,通过连续免疫组织化学和桑格测序,收集治疗前患者的福尔马林固定石蜡包埋块,并将其分为POLE突变型、MMR-D、p53wt和p53abn亚型。主要结局是FPT后的完全缓解率。我们机构纳入了13例患者,其中3例(3/13)为MMR-D,0例(0/13)为POLE突变型,8例(8/13)为p53wt,1例(1/13)为p53abn,1例(1/13)因DNA扩增失败。6例(6/8)p53wt患者、2例(2/3)MMR-D患者和1例(1/1)p53abn患者在治疗后6个月实现了完全缓解。我们的研究结果与已报道的结果最终合并。共有106例接受FPT的患者被纳入。其中,23例(21.7%)被分类为MMR-D,3例(2.8%)为POLE突变型,3例(2.8%)为p53abn,77例(72.6%)为p53wt。FPT后,MMR-D和p53wt亚型之间的完全缓解率(P = 0.152)和复发率(P = 0.174)无显著差异。基于目前的数据,我们观察到ProMisE分类器在接受FPT的EC患者中无预后意义。需要更大规模的前瞻性研究来阐明这种分子分类器在这些病例中的精确预后意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e73d/9160735/a1224f97e5f8/fonc-12-810631-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e73d/9160735/a1224f97e5f8/fonc-12-810631-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e73d/9160735/a1224f97e5f8/fonc-12-810631-g001.jpg

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