结直肠癌中错配修复蛋白表达缺失的意义及其与大鼠肉瘤病毒癌基因、v-Raf小鼠肉瘤病毒癌基因同源物B基因状态相关性研究  

The significance of mismatch repair protein expression deletion in colorectal cancer and its correlation with Ras and v-raf murine sarcoma viral oncogene homolog B1 gene status

作　　者：秦艳[1] 刘彦魁 周心一[1] 金建强[1] 王晓莉[1] 蒋晖[2] 王维佳 高桂花[1] 王振威 齐晓薇[1] Qin Yan;Liu Yankui;Zhou Xinyi;Jin Jianqiang;Wang Xiaoli;Jiang Hui;Wang Weijia;Gao Guihua;Wang Zhenwei;Qi Xiaowei(Department of Pathology,Affiliated Hospital of Jiangnan Univercity,Wuxi 214062,China;Department of Gastrointestinal Surgery,Affiliated Hospital of Jiangnan Univercity,Wuxi 214062,China)

机构地区：[1]江南大学附属医院病理科,无锡214062 [2]江南大学附属医院胃肠外科,无锡214062

出　　处：《中华实验外科杂志》2020年第9期1732-1735,共4页Chinese Journal of Experimental Surgery

基　　金：无锡市青年医学人才(BK20140171);无锡市适宜技术推广项目(T201734)。

摘　　要：目的分析探讨结直肠癌中4种错配修复(MMR)蛋白的表达及其临床意义,RAS、鼠类肉瘤滤过性毒菌致癌同源体B1(BRAF)基因状态及其与4种蛋白表达的相关性。方法采用免疫组织化学法检测634例结直肠癌组织中4种MMR蛋白的表达;对存在MMR蛋白表达缺失者进行微卫星不稳定(MSI)检测。对其中236例(含缺失组的53例)进行RAS和BRAF基因检测。计数资料组间比较采用χ^2检验。结果634例中53例(8.4%)发生MMR蛋白表达缺失,Mut L同源基因1(MLH1)、PMS2、人类MutS同源蛋白2(MSH2)和人类MutS同源蛋白6(MSH6)蛋白表达缺失率分别4.4%(28/634)、4.7%(30/634)、3.3%(21/634)、3.6%(23/634)。缺失组的53例进行MSI分子检测,其中49例(92.4%)出现2~5个位点微卫星不稳定,为MSI-H。236例(含缺失组的53例)结直肠癌RAS和BRAF基因检测结果显示,BRAF基因V600E突变11例,均为微卫星稳定(pMMR);v-Ki-ras2大鼠Kirsten肉瘤病毒基因同源基因(KRAS)基因突变109例,其中7例为错配修复基因缺陷(dMMR);NRAS基因2号外显子检测到突变8例,均为pMMR。结论MMR蛋白表达缺失组多发生于右半结肠,组织学分化差且常伴有粘液成分,肿瘤组织间可见显著的淋巴细胞浸润,患病年龄偏低。KRAS基因状态影响MMR蛋白表达。Objective To evaluate the expression of four mismatch repair(MMR)proteins in colorectal cancer and their relationship with clinical pathological features of patients,as well as the RAS and v-raf murine sarcoma viral oncogene homolog B1(BRAF)gene status in colorectal cancer and their correlation with four MMR protein expression.Methods The expression of four MMR proteins in 634 cases of colorectal cancer was detected by immunohistochemistry.Microsatellite instability(MSI)detection was performed on those with MMR protein expression loss.The RAS and BRAF genes were detected in 236 cases(including 53 cases in dMMR group).Statistical analysis was performed,and the rate was compared by chi-square test.Results In 634 cases,53 cases(8.4%)had MMR protein loss,and the loss rates of MLH1,PMS2,MSH2 and MSH6 protein were 4.4%(28/634),4.7%(30/634),3.3%(21/634)and 3.6%(23/634),respectively MSI molecular detection was performed in 53 cases of dMMR group,and MSI-H was found in 49 cases(92.4%).The results of RAS and BRAF gene detection in 236 cases of colorectal cancer showed that 11 cases of BRAF gene V600E mutation were pMMR;109 cases of KRAS gene mutation,of which 7 cases were dMMR;Eight mutations were detected in exon 2 of NRAS gene,all of which were pMMR.Conclusion The MMR protein expression loss group mostly occurred in the right colon,histologically poorly differentiated and often accompanied by mucus components,significant lymphocyte infiltration can be seen in the tumor tissue,and the age of disease was relatively low.The KRAS gene status affects the expression of MMR protein.

关 键 词：结直肠癌 错配修复 微卫星不稳定 v-Ki-ras2大鼠Kirsten肉瘤病毒基因同源基因 NRAS 鼠类肉瘤滤过性毒菌致癌同源体B1 

分 类 号：R735.34[医药卫生—肿瘤]