结直肠癌新辅助化疗与微卫星不稳定相关性研究  

Correlation between mismatch repair genes in colorectal cancer and neoadjuvant chemotherapy

作　　者：常静[1] 刘继红[2] 强玲 纪志鹏[4] 杨香山[5] 冯斌[1] CHANG Jing;LIU Ji-hong;QIANG Ling;JI Zhi-peng;YANG Xiang-shan;FENG Bin(Affiliated Hospital of Shandong Academy of Medical Sciences,J inan 250031,P.R.China;Tenth Internal Medicine,Shandong Cancer Hospital Affiliated to Shandong University,Shandong Academy of Medical Sciences,Jinan 250117,P.R.China;Department of General Surgery,Second Qilu Hospital of Shandong University,J inan 250006,P.R.China)

机构地区：[1]山东省医学科学院附属医院肿瘤内科,山东济南250031 [2]山东省医学科学院附属医院心内科,山东济南250031 [3]山东大学附属山东省肿瘤医院内十科山东省医学科学院,山东济南250117 [4]山东大学第二医院普外科,山东济南250006 [5]山东省医学科学院附属医院病理科,山东济南250031

出　　处：《中华肿瘤防治杂志》2018年第14期1003-1008,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：山东省自然科学基金(ZR2013HL040); 山东省医学科学院医药卫生科技创新工程

摘　　要：目的错配修复(mismatch repair,MMR)基因表达异常导致的微卫星不稳定(microsatellite instability,MSI)是Ⅱ期结直肠癌预后良好指标,也是对氟脲嘧啶类药物不敏感的预测因素,但与Ⅲ~Ⅳ期结直肠癌患者新辅助治疗的关系不明确。本研究通过检测MMR蛋白(PMS2、MLH1、MSH2和MSH6)在Ⅲ~Ⅳ期结直肠癌新辅助化疗前后的表达情况,探讨MMR蛋白和微卫星不稳定性与Ⅲ~Ⅳ期结直肠癌新辅助化疗之间的关系。方法收集2013-11-01-2015-11-30山东省医学科学院附属医院经病理确诊的Ⅲ~Ⅳ期结直肠癌患者72例,应用FOLFOX6方案进行新辅助化疗后给予手术治疗,用免疫组织化学法分别检测初诊活检组织和治疗后手术标本PMS2、MLH1、MSH2和MSH6表达,分析其表达情况和微卫星不稳定性对新辅助化疗的影响,并分析MMR蛋白和微卫星状态在化疗前后的变化,以及与年龄、分期、病理化疗反应和分化程度的关系。结果 72例Ⅲ~Ⅳ期结直肠癌新辅助化疗前PMS2、MLH1、MSH2和MSH6缺失率分别为15.3%、11.1%、2.8%和6.9%,与化疗反应无关,P值分别为1.000、0.741、1.000和0.389;化疗前MSI发生率为19.4%,较微卫星稳定(microsatellite stability,MSS)有更好的新辅助化疗疗效,P<0.001。与女性相比,男性有更好的新辅助化疗疗效,P=0.009。新辅助化疗后PMS2、MLH1、MSH2和MSH6缺失率分别为22.2%、15.3%、9.7%和11.1%,MSI化疗后发生率为29.2%,较化疗前有升高趋势,但差异无统计学意义,P>0.05。多因素分析显示,分化程度(P=0.042)和性别(P=0.013)是影响新辅助化疗疗效的独立危险因素。结论Ⅲ~Ⅳ期结直肠癌患者中MSI预示较好的新辅助化疗疗效,微卫星状态可作为Ⅲ~Ⅳ期结直肠癌患者新辅助化疗疗效的预测指标。OBJECTIVE Mismatch Repair（MMR）gene mutations can develop microsatellite instability（MSI）.MSI status is applied to predict the well prognosis and poor chemosensitivity in stageⅡcolorectal cancer patients.But its relationship with stageⅢ-Ⅳ colorectal cancer through neoadjuvant chemotherapy are limited.Mismatch repair genes can predict the prognosis and chemosensitivity in stageⅡcolorectal cancer patients,but its relationship with advanced colorectal cancer is unclear.This study analyzed the changes of mismatch repair genes before and after neoadjuvant chemotherapy in advanced colorectal cancer,and discussed the correlation between mismatch repair genes,MSI and neoadjuvant chemotherapy.METHODS MMR protein（PMS2,MLH1,MSH2,MSH6）expression was measured in both pretreatment biopsies and pathologic specimens from 72 patients with advanced colorectal cancer who underwent conversion therapy by FOLFOX regimens and surgery.The influence of the MMR protein expressions,MSI on neoadjuvant chemotherapy was investigated.Changes of mismatch repair genes before and after chemotherapy and correlation between mismatch repair genes and ages,disease staging,chemotherapy response,differentiation were analyzed.RESULTS Before neoadjuvant chemotherapy,the deficiency rate of PMS2,MLH1,MSH2 and MSH6 was respectively 15.3%,11.1%,2.8% and 6.9%in 72 cases of stageⅢ-Ⅳcolorectal cancer,and there was no significant correlation between the chemotherapy response（Pvalues were 1.000,0.741,1.000 and 0.389,respectively）.Before neoadjuvant chemotherapy,the incidence of MSI was19.4%,compared with MSS,there was better efficacy of neoadjuvant chemotherapy（P〈0.001）.Compared with women,men had better efficacy of neoadjuvant chemotherapy（P=0.009）.After neoadjuvant chemotherapy,the deficiency rates of PMS2,MLH1,MSH2 and MSH6 were respectively 22.2%,15.3%,9.7% and 11.1%.The incidence of MSI was29.2%.There was a trend of increase compared with that before chemotherapy,but there was no significant difference between them（P〈

关 键 词：错配修复 微卫星不稳定 结直肠癌 新辅助化疗 

分 类 号：R735.3[医药卫生—肿瘤]