微卫星不稳定性及错配修复蛋白表达与结直肠癌化疗疗效相关性的研究  

The correlation between chemotherapy effects of colorectal cancer and microsatellite instability and mismatch repair

作　　者：冯强[1] 孙琦 孙霞[2] 吴丹[2] 秦磊[3] FENG Qiang;SUN Qi;SUN Xia;WU Dan;QIN Lei(Anorectal Surgery,the Affiliated Jiangyin Hospital of Southeast University Medical College,Jiangyin 214400,China;Oncology Department,the Affiliated Jiangyin Hospital of Southeast University Medical College,Jiangyin 214400,China;General Surgery,the First Affiliated Hospital of Soochow University,Suzhou 215000,China)

机构地区：[1]东南大学医学院附属江阴医院肛肠外科,江苏江阴214400 [2]东南大学医学院附属江阴医院肿瘤科,江苏江阴214400 [3]苏州大学附属第一医院普通外科,江苏苏州215000

出　　处：《东南大学学报（医学版）》2020年第6期793-799,共7页Journal of Southeast University(Medical Science Edition)

摘　　要：目的:探讨结直肠癌(CRC)中错配修复(MMR)蛋白表达及微卫星不稳定(MSI)分型情况,验证MMR蛋白表达与MSI分型的一致性。通过观察不同MSI分型患者采用不同化疗方案的疗效,评估MSI不同分型与不同化疗方案的相关性。方法:运用免疫组化法(IHC)检测130例CRC组织标本中MMR蛋白的表达情况,同时采用荧光聚合酶链反应(PCR)法检测肠癌组织中MSI的分型情况,验证MMR蛋白表达与MSI分型的一致性,进一步分析MSI表达与临床病理特征的相关性。最后根据回顾性研究,观察采用不同化疗方案的不同分期、不同MSI分型患者无进展生存期(PFS)之间的差异,以验证不同MSI分型与不同化疗药物疗效之间的相关性。结果:CRC组织中MMR蛋白表达缺失(dMMR)率为26.9%(35/130),MSI中微卫星高度不稳定性(MSI-H)表达的检出率为23.8%(31/130)。MMR蛋白的表达与MSI表达之间存在相关性(P<0.001)。MSI分型与年龄(P=0.639)、性别(P=0.378)、部位(P=0.418)、分期(P=0.225)无明显相关性。生存分析提示,FOLFOX4化疗方案中MSI-H组患者的复发时间要短于非MSI-H组,而XELOX方案化疗组及未治疗组均未看到MSI-H组与非MSI-H组之间差异有统计学意义。结论:MMR蛋白表达水平与MSI状态有高度的一致性,因此免疫组化方法可用作一线筛查;对于有化疗指征的MSI-H型患者更推荐XELOX方案的化疗。Objective:To investigate the relationship between the expression of mismatch repair(MMR)protein and the microsatellite instability(MSI)typing in colorectal cancer(CRC)by studying the expression of MMR and MSI in colorectal cancer.We evaluate the correlation between different MSI subtypes and different chemotherapy regimens by PFS.Methods:We examined MMR protein expression levels in 130 cases of colorectal cancer using immunohistochemistry(IHC),characterized MSI typing by fluorescence polymerase chain reaction(PCR),confirmed correlations between MMR protein expression and the MSI typing,and analyzed for the correlation between MSI expression and clinicopathological characteristics.Based on the retrospective study,we analyzed the difference of progression free survival(PFS)between patients with different MSI classification and different chemotherapy drugs.Results:The rate of MMR deletion(dMMR)was 26.9%(35/130),and the detection rate of MSI-H was 23.8%(31/130).There was a correlation between MMR protein expression and MSI expression(P<0.001).MSI type had no significant correlation with age(P=0.639),gender(P=0.378),location(P=0.418),or stage(P=0.225).Survival analysis showed that the recurrence time of the MSI-H group was less than that of the non-MSI-H group for the FOLFOX4 regimen,while no statistical difference between the MSI-H group and the non-MSI-H group was found in the XELOX chemotherapy group and the untreated group.Conclusion:The expression level of MMR protein is highly consistent with the status of MSI,suggesting that immunohistochemistry may be used as a preliminary screening method.For MSI-H patients with indications of chemotherapy,XELOX chemotherapy is recommended.

关 键 词：结直肠癌 错配修复 微卫星不稳定 相关性分析 

分 类 号：R735.3[医药卫生—肿瘤]