Brian M Slomovitz, Natalie Danziger, Julia C F Quintanilha, Andrew D Kelly, Gerald Li, Vivek Podder, Douglas I Lin, Ryon P Graf, Julia A Elvin, Thomas J Herzog
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Time to next treatment and overall survival were compared between molecular subtypes, with multivariable Cox models adjusted for relevant covariables.</p><p><strong>Results: </strong>Of 1,139 evaluated patients with advanced or recurrent endometrial carcinoma, the prevalence of the 4 molecular subtypes was 1% POLEmut, 22% high microsatellite instability, 47% TP53mut, and 31% NSMP. Compared with NSMP patients, POLEmut patients had numerically more favorable time to next treatment (HR 0.50, 95% CI 0.21 to 1.21) and overall survival (HR 0.52, 95% CI 0.17 to 1.66). High microsatellite instability patients had similar time to next treatment (HR 1.08, 95% CI 0.89 to 1.30) and overall survival (HR 0.91, 95% CI 0.71 to 1.19) relative to NSMP patients. TP53mut patients had the least favorable outcomes for time to next treatment (compared with NSMP, HR 1.39, 95% CI 1.19 to 1.62) and overall survival (HR 2.15, 95% CI 1.77 to 2.61). In multivariable analysis, TP53mut status was associated with less favorable time to next treatment and overall survival. Frequencies of other biomarkers varied by molecular subtype.</p><p><strong>Conclusions: </strong>The Cancer Genome Atlas (TCGA)/Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) molecular classifier for endometrial carcinoma can be recapitulated using CGP and provides prognostic stratification even within an advanced or recurrent disease cohort. CGP for molecular subclassification could support trial design and enrollment and inform treatment escalation or selection.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"35 10","pages":"102107"},"PeriodicalIF":4.7000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Validation of comprehensive genomic profiling for prognostic and potential therapeutic molecular classification of endometrial cancer.\",\"authors\":\"Brian M Slomovitz, Natalie Danziger, Julia C F Quintanilha, Andrew D Kelly, Gerald Li, Vivek Podder, Douglas I Lin, Ryon P Graf, Julia A Elvin, Thomas J Herzog\",\"doi\":\"10.1016/j.ijgc.2025.102107\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>We sought to validate the prognostic utility of comprehensive genomic profiling (CGP)-based molecular stratification for patients with endometrial carcinoma and to assess co-occurring biomarkers across subtypes.</p><p><strong>Methods: </strong>This study included patients from a de-identified nationwide (US-based) endometrial cancer clinicogenomic database who underwent CGP testing as part of routine care. Molecular subtypes were classified as POLE mutated (POLEmut), MSI-H, TP53 mutated (TP53mut), and no specific molecular profile (NSMP). Time to next treatment and overall survival were compared between molecular subtypes, with multivariable Cox models adjusted for relevant covariables.</p><p><strong>Results: </strong>Of 1,139 evaluated patients with advanced or recurrent endometrial carcinoma, the prevalence of the 4 molecular subtypes was 1% POLEmut, 22% high microsatellite instability, 47% TP53mut, and 31% NSMP. Compared with NSMP patients, POLEmut patients had numerically more favorable time to next treatment (HR 0.50, 95% CI 0.21 to 1.21) and overall survival (HR 0.52, 95% CI 0.17 to 1.66). High microsatellite instability patients had similar time to next treatment (HR 1.08, 95% CI 0.89 to 1.30) and overall survival (HR 0.91, 95% CI 0.71 to 1.19) relative to NSMP patients. TP53mut patients had the least favorable outcomes for time to next treatment (compared with NSMP, HR 1.39, 95% CI 1.19 to 1.62) and overall survival (HR 2.15, 95% CI 1.77 to 2.61). In multivariable analysis, TP53mut status was associated with less favorable time to next treatment and overall survival. Frequencies of other biomarkers varied by molecular subtype.</p><p><strong>Conclusions: </strong>The Cancer Genome Atlas (TCGA)/Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) molecular classifier for endometrial carcinoma can be recapitulated using CGP and provides prognostic stratification even within an advanced or recurrent disease cohort. 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引用次数: 0
摘要
目的：我们试图验证基于综合基因组分析（CGP）的分子分层对子宫内膜癌患者的预后效用，并评估不同亚型的共同发生的生物标志物。方法：本研究纳入了来自去识别的全国（美国）子宫内膜癌临床基因组数据库的患者，这些患者接受了CGP检测作为常规护理的一部分。分子亚型分为POLE突变（POLEmut）、MSI-H、TP53突变（TP53mut）和无特异性分子谱（NSMP）。采用多变量Cox模型对相关协变量进行调整，比较分子亚型之间的下一次治疗时间和总生存期。结果：在1139例晚期或复发性子宫内膜癌患者中，4种分子亚型的患病率为POLEmut占1%，高微卫星不稳定性占22%，TP53mut占47%，NSMP占31%。与NSMP患者相比，POLEmut患者有更有利的下一次治疗时间（HR 0.50, 95% CI 0.21至1.21）和总生存期（HR 0.52, 95% CI 0.17至1.66）。相对于NSMP患者，高微卫星不稳定患者与下一次治疗的时间相似（HR 1.08, 95% CI 0.89至1.30），总生存期（HR 0.91, 95% CI 0.71至1.19）。TP53mut患者在下一次治疗的时间（与NSMP相比，HR 1.39, 95% CI 1.19至1.62）和总生存期（HR 2.15, 95% CI 1.77至2.61）方面的预后最差。在多变量分析中，TP53mut状态与较差的下一次治疗时间和总生存期相关。其他生物标志物的频率因分子亚型而异。结论：癌症基因组图谱(TCGA)/子宫内膜癌前瞻性分子风险分类器（ProMisE）子宫内膜癌分子分类器可以使用CGP进行总结，甚至可以在晚期或复发疾病队列中提供预后分层。分子亚分类的CGP可以支持试验设计和入组，并为治疗升级或选择提供信息。
Validation of comprehensive genomic profiling for prognostic and potential therapeutic molecular classification of endometrial cancer.
Objective: We sought to validate the prognostic utility of comprehensive genomic profiling (CGP)-based molecular stratification for patients with endometrial carcinoma and to assess co-occurring biomarkers across subtypes.
Methods: This study included patients from a de-identified nationwide (US-based) endometrial cancer clinicogenomic database who underwent CGP testing as part of routine care. Molecular subtypes were classified as POLE mutated (POLEmut), MSI-H, TP53 mutated (TP53mut), and no specific molecular profile (NSMP). Time to next treatment and overall survival were compared between molecular subtypes, with multivariable Cox models adjusted for relevant covariables.
Results: Of 1,139 evaluated patients with advanced or recurrent endometrial carcinoma, the prevalence of the 4 molecular subtypes was 1% POLEmut, 22% high microsatellite instability, 47% TP53mut, and 31% NSMP. Compared with NSMP patients, POLEmut patients had numerically more favorable time to next treatment (HR 0.50, 95% CI 0.21 to 1.21) and overall survival (HR 0.52, 95% CI 0.17 to 1.66). High microsatellite instability patients had similar time to next treatment (HR 1.08, 95% CI 0.89 to 1.30) and overall survival (HR 0.91, 95% CI 0.71 to 1.19) relative to NSMP patients. TP53mut patients had the least favorable outcomes for time to next treatment (compared with NSMP, HR 1.39, 95% CI 1.19 to 1.62) and overall survival (HR 2.15, 95% CI 1.77 to 2.61). In multivariable analysis, TP53mut status was associated with less favorable time to next treatment and overall survival. Frequencies of other biomarkers varied by molecular subtype.
Conclusions: The Cancer Genome Atlas (TCGA)/Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) molecular classifier for endometrial carcinoma can be recapitulated using CGP and provides prognostic stratification even within an advanced or recurrent disease cohort. CGP for molecular subclassification could support trial design and enrollment and inform treatment escalation or selection.
期刊介绍：
The International Journal of Gynecological Cancer, the official journal of the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology, is the primary educational and informational publication for topics relevant to detection, prevention, diagnosis, and treatment of gynecologic malignancies. IJGC emphasizes a multidisciplinary approach, and includes original research, reviews, and video articles. The audience consists of gynecologists, medical oncologists, radiation oncologists, radiologists, pathologists, and research scientists with a special interest in gynecological oncology.
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