Wang X W, Lin J, Chen H, Yu F, Zhang H L, Wang Y, Jiang R Y, Wang B, Zhong D R
Department of Pathology, China-Japan Friendship Hospital, Beijing100029, China.
Zhonghua Zhong Liu Za Zhi. 2025 Jan 23;47(1):100-107. doi: 10.3760/cma.j.cn112152-20231024-00225.
To analyze the clinical significance of molecular classification and hereditary phenotype in endometrial carcinoma (EC) based on high throughput sequencing (NGS). 97 EC samples were collected retrospectively from December 2019 to October 2022 in China-Japan Friendship Hospital. NGS technique was used to analyze the molecular classification, POLE hypermutation, microsatellite high Instability/mismatch repair dysfunction (MSI-H/MMRd), P53 protein abnormality (P53 abn), and non-specific molecular profile (NSMP). Lynch syndrome related genes and genes were detected by NGS and their genetic characteristics were analyzed. Of the 97 EC cases, 77 were endometrial adenocarcinoma and 20 were other pathological subtypes. The proportions of the four molecular subtypes were 9.3% (9/97) POLE hypermutation, 16.5% (16/97) MSI-H, 17.5% (17/97) P53 abn and 56.7% (55/97) NSMP, respectively. There were significant differences in age, histological type, lymph node metastasis, pathological stage and other parameters among the four molecular types (＜0.05). 8.2% (8/97) were multiple molecular typing and four multiple molecular typings detected, including POLEmut-MSI-H, POLEmut-P53abn, MSI-H-P53abn, P53abn-P53abn, which accounted for 1.0% (1/97), 3.1% (3/97), 1.0% (1/97) and 3.1% (3/97), respectively. The consistent rate of MSI-H and MMR protein expression was 92.9% (=0.818, ＜0.001). The coincidence rate between gene sequencing and P53 protein expression was 88.9% (=0.661, ＜0.001). In MSI-H type, 25.0% (4/16) were diagnosed as Lynch syndrome, and 75.0% (12/16) were diagnosed as Lynch like syndrome. 7.2% (7/97) somatic variation was detected, while germline variation was not detected in 97 cases. EC molecular classification has feasibility and clinical value. High throughput sequencing can detect low frequency mutations of gene, suggesting that it can provide more accurate molecular information and more accurate molecular typing effect. It is suggested to further detect Lynch syndrome related genes in patients with MSI-H, so as to carry out genetic management for patients and their families and achieve better therapeutic effect.
基于高通量测序（NGS）分析子宫内膜癌（EC）分子分类及遗传表型的临床意义。2019年12月至2022年10月期间，在中国-日本友好医院回顾性收集了97例EC样本。采用NGS技术分析分子分类、POLE超突变、微卫星高度不稳定/错配修复功能障碍（MSI-H/MMRd）、P53蛋白异常（P53 abn）和非特异性分子谱（NSMP）。通过NGS检测林奇综合征相关基因及其他基因，并分析其遗传特征。97例EC病例中，77例为子宫内膜腺癌，20例为其他病理亚型。四种分子亚型的比例分别为9.3%（9/97）POLE超突变、16.5%（16/97）MSI-H、17.5%（17/97）P53 abn和56.7%（55/97）NSMP。四种分子类型在年龄、组织学类型、淋巴结转移、病理分期等参数上存在显著差异（＜0.05）。8.2%（8/97）为多重分子分型，共检测到四种多重分子分型，包括POLEmut-MSI-H、POLEmut-P53abn、MSI-H-P53abn、P53abn-P53abn，分别占1.0%（1/97）、3.1%（3/97）、1.0%（1/97）和3.1%（3/97）。MSI-H与MMR蛋白表达的一致性率为92.9%（=0.818，＜0.001）。基因测序与P53蛋白表达的符合率为88.9%（=0.661，＜0.001）。在MSI-H型中，25.0%（4/16）被诊断为林奇综合征，75.0%（12/16）被诊断为林奇样综合征。97例中检测到7.2%（7/97）的体细胞变异，未检测到生殖系变异。EC分子分类具有可行性和临床价值。高通量测序可检测基因的低频突变，表明其能提供更准确的分子信息和更准确的分子分型效果。建议对MSI-H患者进一步检测林奇综合征相关基因，以便对患者及其家系进行遗传管理，取得更好的治疗效果。
