临床与病理杂志2025，Vol.45Issue(9)：1106-1113,8.DOI:10.11817/j.issn.2095-6959.2025.250520
云南单中心回顾性队列研究:基于高通量测序的子宫内膜癌分子分型及其与临床病理特征的关系
Yunnan single-center retrospective cohort study:Molecular typing of endometrial carcinoma based on high-throughput sequencing and its relationship with clinical pathological features
摘要
Abstract
Objective:With the widespread adoption of high-throughput sequencing(NGS),molecular classification models based on key driver genes and signaling pathways have rapidly evolved,providing a solid foundation for precision medicine.This study aims to evaluate the clinical utility of NGS in the molecular classification of endometrial carcinoma and to preliminarily analyze the clinicopathological characteristics associated with different molecular subtypes,thereby offering insights for individualized treatment strategies. Methods:A total of 497 patients who underwent molecular classification testing for endometrial carcinoma at the Molecular Diagnosis Center of the Third Affiliated Hospital of Kunming Medical University between December 2020 and November 2023 were retrospectively reviewed.After excluding 34 patients with incomplete clinical information or inadequate sample quality,463 patients were included.NGS was used to detect mutations in BRCA1/2,POLE,and TP53,as well as the microsatellite instability(MSI)status in tumor tissues.Based on the World Health Organization(WHO)molecular classification criteria,patients were categorized into the POLE-mutated,microsatellite instability-high(MSI-H),non-specific molecular profile(NSMP),and TP53-mutated subtypes.Clinical data were collected to analyze associations between molecular subtypes and clinicopathological characteristics. Results:The POLE-mutated subtype accounted for 65(14.04%,65/463)patients;the most frequent mutations were c.857C>G in exon 9 and c.1231G>T/C in exon 13,representing 64.6%of all POLE mutation sites.Among these,6 patients also exhibited MSI-H,and 19 patients harbored concurrent TP53 mutations.The MSI-H subtype comprised 113(24.40%,113/463)patients,including 19 patients with co-existing TP53 mutations.The NSMP subtype includes 227(49.03%,228/463)patients.The TP53-mutated subtype consisted of 58(12.53%,58/463)patients.Significant differences were observed among the 4 molecular subtypes in age distribution(adjusted P=0.021),histological differentiation(adjusted P=0.002),International Federation of Gynecology and Obstetrics(FIGO)stage(adjusted P=0.002),and lymph node metastasis rate(adjusted P=0.002).No significant differences were found in ethnicity,family history,histological type,depth of myometrial invasion,and lymphovascular space invasion(LVSI)after adjustment(all P>0.05).Patients with POLE-mutated tumors were characterized by age<60 years,the highest proportion of FIGO stage I,and the lowest lymph node metastasis rate,whereas the TP53-mutated subtype was associated with age≥60 years,moderate-to-poor differentiation,a higher proportion of FIGO stage III-IV,and the highest lymph node metastasis rate. Conclusion:NGS enables the parallel detection of multiple driver gene mutations and MSI status in a single assay,allowing comprehensive molecular classification of endometrial cancer.Significant differences among the 4 molecular subtypes in age,differentiation,FIGO stage,and lymph node metastasis suggest that molecular classification has important clinical utility in postoperative risk stratification and therapeutic decision-making.关键词
子宫内膜癌/分子分型/高通量测序/POLE基因/微卫星不稳定性/TP53基因Key words
endometrial carcinoma/molecular classification/next-generation sequencing/POLE gene/microsatellite instability/TP53 gene引用本文复制引用
CAI Jingjing,LI Zhuoying,LIU Xin,WANG Xiaoxiong,ZHOU Jinyi,YANG Ruijiao,WU Shunxian,ZHOU Yongchun..云南单中心回顾性队列研究:基于高通量测序的子宫内膜癌分子分型及其与临床病理特征的关系[J].临床与病理杂志,2025,45(9):1106-1113,8.基金项目
云南省教育厅科学研究基金(FWCY-ZNT2024012) （FWCY-ZNT2024012）
吴阶平医学基金会资助项目(320.6750.2024-24-3).This work was supported by the Education Science Research Fund of Yunnan Provincial Department of Education(FWCY-ZNT2024012)and the WU Jieping Medical Foundation(320.6750.2024-24-3),China. （320.6750.2024-24-3）
