错配修复蛋白表达及RAS基因突变与结直肠癌临床病理特征的关系

Correlation of the expression of mismatch repair proteins and RAS mutation with clinicopathological parameters in colorectal carcinoma

目的探讨结直肠癌组织中错配修复(mismatch repair,MMR)蛋白表达及RAS基因突变状态与临床病理特征的相关性。方法采用免疫组化法检测186例结直肠癌组织中4种MMR蛋白(MSH2、MSH6、MLH1、PMS2)的表达,并采用ARMS-PCR法检测RAS基因突变状态。结果186例结直肠癌组织中MMR蛋白表达缺失率为6.99%(13/186),其中MSH2和MSH6共同缺失2例,MLH1和PMS2共同缺失9例,MSH6单独缺失1例,PMS2单独缺失1例。RAS突变者97例(52.15%),其中KRAS突变88例(47.31%),NRAS突变9例(4.84%)。MMR蛋白表达缺失多发生于50岁以下、肿瘤部位多为右半结肠、黏液腺癌、肿瘤低分化、肿瘤分期Ⅰ+Ⅱ期的患者(P<0.05)。RAS突变状态与结直肠癌临床病理特征无相关性(P>0.05)。MMR蛋白表达缺失病例中,RAS突变状态与肿瘤是否伴黏液腺癌成分有显著相关性(P=0.015),伴RAS突变病例不伴有黏液腺癌,而RAS野生型多伴黏液腺癌。结论MMR蛋白表达状态与结直肠癌患者年龄、肿瘤部位、分化程度、肿瘤分期和病理分型有关,结合RAS突变检测,可为结直肠癌患者的个体化治疗提供更多的依据。

Purpose To investigate the association between the expression of mismatch repair(MMR)proteins and RAS mutations with clinicopathological characteristics of colorectal carcinoma.Methods Immunohistochemical staining was performed to identify the expression of MMR proteins(MSH2,MSH6,MLH1,and PMS2)in 186 colorectal carcinoma tissues.ARMS-PCR was performed to detect RAS gene mutations.Results The total deficiency rate of MMR proteins was 6.99%(13/186),in which 2 cases showed combined deficiency of MSH2 and MSH6,9 cases showed combined deficiency of MLH1 and PMS2,1 case showed MSH6 deficiency and 1 case showed PMS2 deficiency.RAS gene mutation rate was 52.15%(97/186),with a KRAS mutation rate of 47.31%(88/186)and NRAS mutation rate of 4.84%(9/186),respectively.The MMR protein deficiency happened more frequently in patients under 50 years old,with tumor at the right colon,with mucinous adenocarcinoma,poor differentiation,or tumor stageⅠ+Ⅱ(P<0.05).There was no significant correlation between RAS status and clinicopathological characteristics of colorectal carcinoma(P>0.05).In the MMR protein expression deficiency group,RAS status had a significant statistical difference between the tumors with mucinous adenocarcinoma component and without(P=0.015):cases with RAS gene mutation had no mucinous adenocarcinoma components,but most of the cases without RAS gene mutation had mucinous adenocarcinoma components.Conclusion MMR protein deficiency is associated with patients’age,tumor location,tumor differentiation,clinical stage and histopathological typing.Detection of RAS gene mutation and MMR protein status may give more precise individualized treatment for colorectal carcinoma patients.