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低分期、低级别子宫内膜样型子宫内膜癌早期复发的基因组决定因素。

Genomic Determinants of Early Recurrences in Low-Stage, Low-Grade Endometrioid Endometrial Carcinoma.

机构信息

Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

出版信息

J Natl Cancer Inst. 2022 Nov 14;114(11):1545-1548. doi: 10.1093/jnci/djac119.

Abstract

Low-stage, low-grade endometrioid endometrial carcinoma (EEC), the most common histologic type of endometrial cancer, typically has a favorable prognosis. A subset of these cancers, however, displays an aggressive clinical course with early recurrences, including distant relapses. All statistical tests were 2-sided. Using a combination of whole-exome and targeted capture sequencing of 65 FIGO stage IA and IB grade 1 EECs treated with surgery alone, we demonstrate that chromosome 1q gain (odds ratio [OR] = 8.09, 95% confidence interval [CI] = 1.59 to 54.6; P = .02), PIK3CA mutation (OR = 9.16, 95% CI = 1.95 to 61.8; P = .01), and DNA mismatch repair-deficient molecular subtype (OR = 7.92, 95% CI = 1.44 to 87.6; P = .02) are independent predictors of early recurrences within 3 years in this patient population. Chromosome 1q gain was validated in an independent dataset of stage I grade 1 EECs subjected to whole-exome sequencing. Our findings expand on the repertoire of genomic parameters that should be considered in the evaluation of patients with low-stage, low-grade EEC.

摘要

低分期、低分级子宫内膜样腺癌(EEC)是子宫内膜癌最常见的组织学类型,通常具有良好的预后。然而,这些癌症中的一部分具有侵袭性的临床病程,包括早期复发和远处转移。所有统计检验均为双侧检验。通过对 65 例接受单纯手术治疗的 FIGO 分期 IA 和 IB 级 1 型 EEC 患者进行全外显子组和靶向捕获测序的组合分析,我们证实染色体 1q 增益(优势比 [OR] = 8.09,95%置信区间 [CI] = 1.59 至 54.6;P =.02)、PIK3CA 突变(OR = 9.16,95% CI = 1.95 至 61.8;P =.01)和 DNA 错配修复缺陷分子亚型(OR = 7.92,95% CI = 1.44 至 87.6;P =.02)是该患者人群中 3 年内早期复发的独立预测因子。在接受全外显子组测序的 I 期 1 级 EEC 独立数据集上验证了染色体 1q 增益。我们的研究结果扩展了基因组参数的范围,这些参数在评估低分期、低分级 EEC 患者时应予以考虑。

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