目的：探究淋巴细胞激活基因-3（Lymphocyte activating gene 3，LAG-3）在早期子宫内膜癌（endometrial cancer，EC）中的表达与临床病理特征、预后之间的关系。  

材料与方法：选取2016年1月1日至2018年12月31日期间诊断为子宫内膜样癌并在中国医学科学院肿瘤医院接受子宫内膜癌分期术，且术后病理分期均为I期的患者，收集患者的完整临床病理信息、诊疗数据及预后随访信息进行回顾性分析。对术后肿瘤组织标本采用免疫组化的方法检测 LAG-3在早期EC患者中表达，讨论其与各临床病理特征（分化程度、脉管瘤栓和病理分期等）和预后之间的相关性。

结果：本研究共纳入早期子宫内膜样癌患者157例，其中LAG-3高表达61例，LAG-3低表达96例。LAG-3高表达与分化程度、脉管瘤栓和分期显著相关（p＜0.05）；Spearman相关性分析结果显示，在EC总体队列中，P53与LAG-3表达之间非显著相关（r=-0.035,p=0.667）；在pMMR和dMMR亚组中，P53与LAG-3表达显著相关（r=-0.208,p=0.041）；采用K-M法绘制生存曲线，结果显示高、中、低分化EC患者的无病生存期（Disease Free Survival,DFS）具有显著差异(p=0.039)，总生存期（Overall survival，OS）未见显著差异(p=0.12)；脉管瘤栓阳性与阴性患者的DFS具有显著差异(p=0.02)，OS未见显著差异(p=0.059)； dMMR与pMMR患者的DFS具有显著差异（p=0.018），OS未见显著差异（p=0.914）；dMMR伴LAG-3高表达的早期EC患者与其他组别相比，DFS差异具有统计学意义（p=0.019）。dMMR伴LAG-3高表达组 OS最差，与其他组相比差异无统计学意义（p=0.45）。  以DFS为因变量，将脉管瘤栓、LAG-3表达水平、病理学分期、初治年龄作为自变量，进行Cox回归分析，结果显示，脉管瘤栓是早期EC患者DFS不良的独立危险因素（HR=0.382，95%CI 为0.148～0.983， p=0.046）。

结论： 在早期EC中LAG-3早期EC中存在差异性表达，往往高水平的LAG-3表达与不良预后临床病理特征及预后不良相关；LAG-3表达可能与MMR、P53之间存在间存在相关作用；LAG-3可能成为预测EC预后不良的潜在标志物。

Objective: To explore the expression of Lymphocyte Activating Gene 3 (LAG-3) in early-stage endometrial cancer (EC) and its relationship with clinicopathological features and prognosis.

Materials and Methods: Patients diagnosed with early-stage endometrioid adenocarcinoma at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 1, 2016, and December 31, 2018, who underwent surgical treatment with complete clinical and pathological information, treatment data, and follow-up information, were included for retrospective analysis. Immunohistochemistry was used to detect LAG-3 expression in tumor tissue specimens from early EC patients, and its correlation with various clinical pathological features (differentiation degree, vascular invasion, pathological staging, etc.) and prognosis was discussed.

Results: A total of 157 patients with early-stage endometrioid adenocarcinoma were included, among whom 61 cases showed high LAG-3 expression and 96 cases showed low LAG-3 expression. High LAG-3 expression was significantly associated with differentiation, vascular invasion, and staging (p < 0.05). Spearman correlation analysis showed no significant correlation between P53 and LAG-3 expression in the overall EC cohort (r = -0.035, p = 0.667), but a significant correlation was observed in the pMMR and dMMR subgroups (r = -0.208, p = 0.041). Kaplan-Meier analysis revealed significant differences in disease-free survival (DFS) among patients with high, moderate, and low differentiation EC (p = 0.039), while overall survival (OS) did not show significant differences (p = 0.12). Positive vascular invasion was associated with significant differences in DFS (p = 0.02), but not OS (p = 0.059). Patients with dMMR had significant differences in DFS (p = 0.018), but not OS (p = 0.914). dMMR with high LAG-3 expression in early-stage EC patients showed significant differences in DFS compared to other groups (p = 0.019). However, OS did not significantly differ among groups (p = 0.45). Cox regression analysis with DFS as the dependent variable and vascular invasion, LAG-3 expression level, pathological staging, and age at initial treatment as independent variables showed that vascular invasion was an independent risk factor for poor DFS in early-stage EC patients (HR = 0.382, 95% CI 0.148-0.983, p = 0.046).

Conclusion: LAG-3 exhibits differential expression in early-stage EC, with high levels of LAG-3 expression often associated with adverse clinicopathological features and poor prognosis. LAG-3 expression may be correlated with MMR and P53, and it could serve as a potential marker for predicting poor prognosis in EC.