非小细胞肺癌组织微卫星不稳定与T淋巴细胞浸润的关系

The relationship of microsatellite instability with infiltration of T lymphocytes in tissues of non-small cell lung cancer

目的:分析非小细胞肺癌(non-small cell lung cancer,NSCLC)组织错配修复蛋白MLH1、MSH2和MSH6的表达和T淋巴细胞浸润情况,探讨微卫星不稳定(microsatellite instability,MSI)与NSCLC组织T淋巴细胞浸润的关系。方法:收集天津医科大学肿瘤医院2004年至2010年NSCLC组织标本100例,应用免疫组化法检测癌组织中MLH1、MSH2和MSH6的表达,以其中1种及1种以上蛋白表达阴性者判定为MSI;同时检测T淋巴细胞浸润情况,并分析MSI与NSCLC临床病理特征的关系。结果:NSCLC组织中MSI检出率24%,少于微卫星稳定(microsatellite stability,MSS)。MSI NSCLC组织中T淋巴细胞浸润明显高于MSS者。免疫组化结果显示:MSI NSCLC组织CD3^+、CD4^+、CD8^+ T淋巴细胞浸润数目明显多于MSS NSCLC组织,两者差异有统计学意义(P<0.05)。MSI与患者的年龄有关(P<0.05),而与患者的性别、肿瘤组织类型、肿瘤大小、淋巴结有无转移和肿瘤有无远处转移均无关(P>0.05)。结论:MSI影响NSCLC肿瘤免疫微环境,MSI的检测可为NSCLC免疫治疗效应提供预测指标。

Objective： To analyze expressions of the mismatch repair proteins,MLH1,MSH2 and MSH6,and infiltration of T lymphocytes in tissues of non-small cell lung cancer（ NSCLC） and to explore a relationship of microsatellite instability（ MSI） with infiltration of T lymphocytes in NSCLC. Methods： One hundred samples of NSCLC tissues diagnosed in Cancer Institute and Hospital,Tianjin Medical University between 2004 and 2010 were collected. Expressions of the MLH1,MSH2 and MSH6,and infiltration of T lymphocytes in the carcinoma tissues were examined with immunohistochemical assay. The carcinoma tissues with one negative expression among the above proteins were determined as MSI,and clinical pathologic characteristics of MSI NSCLC were analyzed. Results： Petection rate of MSI in NSCLC tissues was 24%,that was lower than that in MSS. Infiltration of T lymphocytes in the tissues of MSI NSCLC was obviously higher than that in MSS. Results of the immunohistochemical assays showed that numbers of CD3~＋,CD4~＋ and CD8~＋ T lymphocytes infiltrated in the tissues of MSI NSCLC were significantly higher than those in the tissues of MSS NSCLC（ P〈0. 05）. MSI situation in the cases was related with their age（ P〈0. 05） but not with their gender,pathological type of tumor,primary tumor size,involvement of regional lymph node and distant metastasis（ P〉0. 05）. Conclusion： MSI affects the tumor immune microenvironment of NSCLC,which might provide a novel predictive indicator for immunotherapy of NSCLC.