作者
Lanlan Li,H. Li,J Li,X B Zhang,Zhiyong Wang,Danhua Shen,Jianliu Wang
摘要
Objective: To investigate the relationships between molecular types of the cancer genome atlas (TCGA) of patients with endometrial carcinoma (EC) and lymph node metastasis and other clinicopathological features. Methods: The clinical pathological information of 295 patients with EC who underwent initial inpatient surgical treatment and accepted the detection of the molecular types of TCGA with next-generation sequencing technology at Peking University People's Hospital were collected during April 2016 and May 2022. The TCGA molecular typing of EC was divided into four types: POLE-ultramutated (15 cases), high microsatellite instability (MSI-H; 50 cases), copy-number low (CNL; 175 cases), and copy-number high (CNH; 55 cases). The differences of clinical pathological features among different molecular types and the risk factors of lymph node metastasis were analyzed retrospectively. Results: Among 295 patients with EC, the average age was (56.9±0.6) years. (1) There was a statistically significant difference in lymph node metastasis (0, 8.0%, 10.3% and 25.5%) among the four molecular types (χ2=12.524, P=0.006). There were significant differences in age, stage, pathological type, grade (only endometrioid carcinoma), myometrium invasion, lymphatic vascular space infiltration, and estrogen receptor among the EC patients of four molecular types (all P<0.05). Among them, while in the patients with CNH type, the pathological grade was G3, the pathological type was non-endometrioid carcinoma, and the proportion of myographic infiltration depth ≥1/2 were higher (all P<0.05). (2) Univariate analysis suggested that pathological type, grade, myometrium infiltration depth, cervical interstitial infiltration, lymphatic vascular space infiltration, and progesterone receptor were all factors which significantly influence lymph node metastasis (all P<0.01); multivariate analysis suggested that the lymphatic vascular space infiltration was an independent risk factor for lymph node metastasis (OR=5.884, 95%CI: 1.633-21.211; P=0.007). (3) The factors related to lymph node metastasis were different in patients with different molecular types. In the patients with MSI-H, the non-endometrioid carcinoma of pathological type was independent risk factor for lymph node metastasis (OR=29.010, 95%CI: 2.067-407.173; P=0.012). In the patients with CNL, myometrium infiltration depth≥1/2 (OR=4.995, 95%CI: 1.225-20.376; P=0.025), lymphatic vascular space infiltration (OR=14.577, 95%CI: 3.603-58.968; P<0.001) were the independent risk factors for lymph node metastasis. While in the CNH type patients pathological type of non-endometrioid carcinoma (OR=7.451, 95%CI: 1.127-49.281; P=0.037), cervical interstitial infiltration (OR=22.938, 95%CI: 1.207-436.012; P=0.037), lymphatic vascular space infiltration (OR=9.404, 95%CI: 1.609-54.969; P=0.013), were the independent risk factors for lymph node metastasis. Conclusions: POLE-ultramutated EC patients have the lowest risk of lymph node metastasis, and CNH patients have the highest risk of lymph node metastasis. The risk factors of lymph node metastasis of different molecular types are different. According to preoperative pathological and imaging data, lymph node metastasis is more likely to occur in patients with non-endometrioid carcinoma in MSI-H and CNH type patients, and lymph node metastasis is more likely to occur in patients with myometrium infiltration depth ≥1/2 in CNL type patients.目的: 探讨子宫内膜癌(EC)患者癌症基因组图谱(TCGA)分子分型与淋巴结转移及其他临床病理特征的关系。 方法: 收集2016年4月至2022年5月在北京大学人民医院住院行手术治疗且采用二代测序技术进行TCGA分子分型的295例初治EC患者的临床病理资料。EC的TCGA分子分型分为4种,即POLE超突变型(15例)、微卫星不稳定性(MSI-H)型(50例)、低拷贝(CNL)型(175例)和高拷贝(CNH)型(55例)。回顾性分析不同分子分型EC患者的临床病理特征的差异以及淋巴结转移的相关影响因素。 结果: 295例EC患者的年龄为(56.9±0.6)岁。(1)POLE超突变型、MSI-H型、CNL型和CNH型4种分子分型患者的淋巴结转移率(分别为0、8.0%、10.3%和25.5%)比较,差异有统计学意义(χ2=12.524,P=0.006)。4种分子分型EC患者的年龄、手术病理分期、病理类型、子宫内膜样癌病理分级、肌层浸润深度、淋巴脉管间隙浸润比例、雌激素受体表达分别比较,差异均有统计学意义(P均<0.05);其中,CNH型患者的子宫内膜样癌病理分级为G3、病理类型为非子宫内膜样癌、肌层浸润深度≥1/2的比例显著高于其他3种分子分型(P均<0.05)。(2)单因素分析显示,病理类型、子宫内膜样癌病理分级、肌层浸润深度、子宫颈间质浸润、淋巴脉管间隙浸润、孕激素受体表达均为显著影响EC患者淋巴结转移的因素(P均<0.01);多因素分析显示,淋巴脉管间隙浸润是影响EC患者淋巴结转移的独立危险因素(OR=5.884,95%CI为1.633~21.211;P=0.007)。(3)不同分子分型EC患者淋巴结转移的相关影响因素不同。MSI-H型患者中,病理类型为非子宫内膜样癌是影响淋巴结转移的独立危险因素(OR=29.010,95%CI为2.067~407.173;P=0.012);CNL型患者中,肌层浸润深度≥1/2(OR=4.995,95%CI为1.225~20.376;P=0.025)、有淋巴脉管间隙浸润(OR=14.577,95%CI为3.603~58.968;P<0.001)均是影响淋巴结转移的独立危险因素;CNH型患者中,病理类型为非子宫内膜样癌(OR=7.451,95%CI为1.127~49.281;P=0.037)、有子宫颈间质浸润(OR=22.938,95%CI为1.207~436.012;P=0.037)和淋巴脉管间隙浸润(OR=9.404,95%CI为1.609~54.969;P=0.013)均是影响淋巴结转移的独立危险因素。 结论: 分子分型为POLE超突变型的EC患者的淋巴结转移率最低,CNH型患者的淋巴结转移率最高。不同分子分型EC患者的淋巴结转移危险因素不尽相同,根据术前病理检查及影像学检查资料,MSI-H型及CNH型患者中非子宫内膜样癌患者易出现淋巴结转移,CNL患者中肌层浸润深度≥1/2者易出现淋巴结转移。.