Zhao L Y, Dai Y B, Li L W, Wang Z Q, Wang J L
Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.
Zhonghua Fu Chan Ke Za Zhi. 2021 Oct 25;56(10):697-704. doi: 10.3760/cma.j.cn112141-20210811-00443.
To explore the application and clinical significance of the cancer genome atlas (TCGA) molecular classification in endometrial cancer (EC). Sixty-six EC patients collected from December 2018 to March 2021 from Peking University People's Hospital were categorized into four subgroups based on TCGA molecular classification tested by next generation sequencing. The correlation among four molecular subgroups and the clinical-pathological features including prognosis were analyzed. (1) Clinical and pathological features: median age at diagnosis was 56 years (range: 24-78 years). The cases were distributed as follows: 3 (5%) cases DNA polymerase epsilon (POLE) ultra-mutated, 11 (17%) cases high microsatellite instability (MSI-H) including 2 Lynch syndrome, 42 (64%) cases low copy-number (CN-L) and 10 (15%) cases high copy-number (CN-H). There were significant differences among four subtypes in the combination of other tumors, tumor family history, surgical method, International Federation of Gynecology and Obstetrics (FIGO, 2009) stage, depth of muscle invasion and lymph vascular space invasion (all <0.05). The proportions of patients in CN-H subgroup with advanced FIGO stage (stage Ⅲ-Ⅳ), deep muscle invasion and positive lymph-vascular space invasion were significantly increased. There were no significant differences in age, menopausal status, body mass index, metabolic syndrome-related complications, preoperative serum CA and human epididymis protein 4 levels, tumor size, pathological grade (only endometrioid cancer), and lymph node metastasis among the 4 TCGA molecular types (all >0.05). (2) Immuno-related molecular analysis: among 66 EC patients, 27 patients underwent immunohistochemical analysis of programmed cell death 1 ligand 1 (PD-L1) protein, and 28 patients underwent tumor mutation burden (TMB) detection. POLE and MSI-H subgroups contained TMB than those in CN-L and CN-H (<0.05).(3) Prognosis: the median follow-up time was 10 months (range: 0-28 months). The progression-free survival rate of TCGA molecular types were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 80% (CN-H) respectively and had significant differences (=0.034). The overall survival were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 90% (CN-H) respectively, but there were not statistically significant difference (=0.361). POLE ultra-mutated and MSI-H subgroups had the best survival, while CN-H had the worst. TCGA molecular classification has feasibility and clinical value in clinical application of EC, which is helpful to identify the prognosis of patients.
探讨癌症基因组图谱（TCGA）分子分类在子宫内膜癌（EC）中的应用及临床意义。收集2018年12月至2021年3月北京大学人民医院的66例EC患者，基于通过二代测序检测的TCGA分子分类将其分为四个亚组。分析四个分子亚组与包括预后在内的临床病理特征之间的相关性。（1）临床和病理特征：诊断时的中位年龄为56岁（范围：24 - 78岁）。病例分布如下：3例（5%）DNA聚合酶ε（POLE）超突变，11例（17%）高微卫星不稳定性（MSI-H），包括2例林奇综合征，42例（64%）低拷贝数（CN-L），10例（15%）高拷贝数（CN-H）。四个亚型在其他肿瘤合并情况、肿瘤家族史、手术方式、国际妇产科联盟（FIGO，2009）分期、肌层浸润深度和脉管间隙浸润方面存在显著差异（均<0.05）。CN-H亚组中FIGO晚期（Ⅲ - Ⅳ期）、肌层浸润深和脉管间隙浸润阳性的患者比例显著增加。四个TCGA分子类型在年龄、绝经状态、体重指数、代谢综合征相关并发症、术前血清CA和人附睾蛋白4水平、肿瘤大小、病理分级（仅子宫内膜样癌）和淋巴结转移方面无显著差异（均>0.05）。（2）免疫相关分子分析：66例EC患者中，27例进行了程序性细胞死亡1配体1（PD-L1）蛋白的免疫组化分析，28例进行了肿瘤突变负荷（TMB）检测。POLE和MSI-H亚组的TMB高于CN-L和CN-H亚组（<0.05）。（3）预后：中位随访时间为10个月（范围：0 - 28个月）。TCGA分子类型的无进展生存率分别为100%（POLE超突变）、100%（MSI-H）、98%（CN-L）和80%（CN-H）且有显著差异（=0.034）。总生存率分别为100%（POLE超突变）、100%（MSI-H）、98%（CN-L）和90%（CN-H），但无统计学差异（=0.361）。POLE超突变和MSI-H亚组生存率最佳，而CN-H亚组最差。TCGA分子分类在EC的临床应用中具有可行性和临床价值，有助于识别患者的预后。
