Next-generation sequencing outperforms Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) in endometrial cancer molecular classification.

BJC reports Pub Date : 2025-05-20 DOI:10.1038/s44276-025-00145-2

Takuma Yoshimura, Kohei Nakamura, Tatsuyuki Chiyoda, Reika Takamatsu, Ryutaro Kawano, Eriko Aimono, Miho Kawaida, Kensuke Sakai, Yohei Masugi, Hiroshi Nishihara, Wataru Yamagami

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Abstract

Background: We aimed to compare the values of next-generation sequencing (NGS) and Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) in redefining the molecular classification of endometrial cancer (EC).

Methods: We investigated the relationship between clinical outcomes and molecular subtypes of POLE, microsatellite instability-high (MSI-H), copy number low (CN-L), and copy number high (CN-H) classified by cancer gene panel testing for 145 cancer-related genes, as well as the immunohistochemical status of p53 and mismatch repair genes, in 200 cases of EC.

Results: The NGS-based classification identified CN-L subtype as the most prevalent (104/200, 52.0%), followed by MSI-H (38/200, 19.0%), POLE (33/200, 16.5%), and CN-H (25/200, 12.5%). Overall survival differed significantly for the four subtypes based on the NGS (p = 0.006) but not on the ProMisE (p = 0.117) classification. Additional mutations were identified for some POLE subtypes beyond the known hotspots, with 18.2% (6 of 33) showing concurrent MSI-H. Immunohistochemistry showed a p53 wild-type pattern for 12 (48%) CN-H cases, and there was no significant difference in prognosis depending on the p53 status in the CN-H subtype.

Conclusions: NGS surpassed ProMisE in EC molecular classification, offering precise stratification and prognostication. Our NGS platform has the potential to contribute to personalized treatment in EC.

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新一代测序在子宫内膜癌分子分类中优于前瞻性分子风险分类器（Proactive Molecular Risk Classifier for endomecancer, ProMisE）。

背景：我们旨在比较下一代测序（NGS）和子宫内膜癌前瞻性分子风险分类器（ProMisE）在重新定义子宫内膜癌（EC）分子分类中的价值。方法：通过对200例EC患者进行145个癌相关基因的癌基因panel检测，研究其POLE分子亚型、微卫星不稳定性高（MSI-H）、拷贝数低（CN-L）、拷贝数高（CN-H），以及p53和错配修复基因的免疫组化状态与临床结果的关系。结果：ngs分类发现CN-L亚型最常见（104/ 200,52.0%），其次是MSI-H亚型（38/ 200,19.0%）、POLE亚型（33/ 200,16.5%）和CN-H亚型（25/ 200,12.5%）。基于NGS分类的四种亚型的总生存期差异显著（p = 0.006），但基于ProMisE分类的总生存期差异不显著（p = 0.117）。在已知热点之外的一些POLE亚型中发现了额外的突变，其中18.2%（33人中有6人）显示并发MSI-H。免疫组化显示12例（48%）CN-H为p53野生型，CN-H亚型中p53状态的不同对预后无显著影响。结论：NGS在EC分子分类上超越了ProMisE，提供了精确的分层和预测。我们的NGS平台有潜力为EC的个性化治疗做出贡献。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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