非小细胞肺癌组织中DNA错配修复蛋白的表达及与临床病理特征的关系

Expression of DNA mismatch repair proteins and their association with clinical and pathological characteristics in patients with non-small cell lung cancer

目的 探究非小细胞肺癌组织中DNA错配修复(MMR)蛋白表达情况,分析其与患者临床病理特征的关系。方法收集2018年1月至2023年1月嘉兴市第二医院手术切除的216例非小细胞肺癌患者的癌组织标本,采用免疫组化法检测癌组织中4种MMR蛋白(MSH2、MSH6、PMS2、MLH1)的表达情况,分析MMR蛋白表达患者的临床病理特征。结果 216例癌组织中MMR蛋白缺失3例(1.39%),均为MLH1及PMS2阴性、MSH2及MSH6阳性,癌组织周围均见淋巴细胞浸润,其中1例肺癌常规基因检测未检出基因突变;其余213例中MSH2蛋白表达强度与腺癌的不同类型、肿瘤周围淋巴细胞带有关,MSH6蛋白表达强度与腺癌的不同类型、肿瘤内淋巴细胞浸润有关,PMS2蛋白表达强度与肿瘤最大径、肿瘤周围淋巴细胞带有关,差异均有统计学意义(均P<0.05)。MLH1蛋白表达强度与肿瘤最大径、腺癌的不同类型、肿瘤内淋巴细胞浸润、肿瘤周围淋巴细胞带均无关,同时,4种蛋白表达强度与病理分型、淋巴结转移情况及Ki-67也无关。结论 MMR蛋白在非小细胞肺癌中的缺失率较低,可在其他常规基因检测阴性的病例中检出;癌组织周围淋巴细胞浸润提示可能存在MMR蛋白缺失。MMR蛋白表达强度与肿瘤最大径、腺癌的不同类型、肿瘤内淋巴细胞浸润、肿瘤周围淋巴细胞带有关,与病理分型、淋巴结转移情况及Ki-67无关。

Objective To investigate the expression of DNA mismatch repair(MMR)proteins and their association with clinical and pathological characteristics in patients with non-small cell lung cancer(NSCLC).Methods Clinical and pathological data of 216 patients with NSCLC who underwent surgical resection at Jiaxing Second Hospital from January 2018 to January 2023 were retrospectively analyzed.The expression of 4 MMR proteins(MSH2,MSH6,PMS2,MLH1)in tumor tissues was detected by immunohistochemical staining,and the relationship of MMR protein expression with clinical and pathological characteristics of patients was analyzed.Results Among 216 patients,3 cases(1.39%)showed loss of MMR proteins,negative expression of MLH1 and PMS2 and positive expression of MSH2 and MSH6;the lymphocyte infiltration around the tumor was observed in all cases and 1 case did not show any gene mutations in routine genetic testing for lung cancer.Among remaining 213 cases,the intensity of MSH2 protein expression was associated with adenocarcinoma types and lymphocytic infiltration around the tumor,while the intensity of MSH6 protein expression was associated with adenocarcinoma types and lymphocytic infiltration within the tumor;the intensity of PMS2 protein expression was associated with the maximum tumor diameter and lymphocytic infiltration around the tumor(all P<0.05).There was no association between the intensity of MLH1 protein expression and the maximum tumor diameter,adenocarcinoma types,lymphocytic infiltration within the tumor,or lymphocytic infiltration around the tumor.Moreover,the expression levels of these 4 proteins were not associated with pathological classification,lymph node metastasis,or Ki 67 expression.Conclusion There is a low rate of MMR protein loss in NSCLC,which may be detected in cases with negative results in routine genetic testing.Lymphocyte infiltration around tumor tissues in pathological sections suggests the possibility of MMR protein loss.The intensity of MMR protein expression is associated with the maximum tumor diameter,different types of adenocarcinoma,lymphocytic infiltration within the tumor,and lymphocytic infiltration around the tumor,but not with pathological classification,lymph node metastasis,or Ki-67.