摘要目的 分析结直肠癌前病变与结直肠腺癌免疫表型及基因突变特征,比较两种结直肠癌前病变癌变机制的差异.方法 收集2006年1月至2012年6月间诊断的53例结直肠锯齿状病变,包括30例增生性息肉、20例广基锯齿状腺瘤(SSA)及3例混合性息肉；同时选取45例传统腺瘤、50例结直肠腺癌.采用免疫组织化学EnVision法检测30例增生性息肉、20例SSA、3例混合性息肉以及45例传统腺瘤DNA错配修复(MMR)蛋白MLH1、MSH2、MSH6及甲基转移酶MGMT蛋白的表达情况；采用Sanger直接测序法检测10例SSA、10例传统腺瘤、l例混合性息肉及50例结直肠腺癌中KRAS、BRAF及PIK3CA基因的突变情况.结果 (1)MLH1蛋白在增生性息肉中仅3例阴性(10％),在SSA、传统腺瘤中均呈阳性.MSH2、MSH6及MGMT蛋白在增生性息肉及SSA中的阴性率明显高于传统腺瘤,差异均具有统计学意义(P＜O.01).(2)结直肠SSA和传统腺瘤中KRAS基因突变比例为5/10,5/10；1例混合性息肉存在KRAS基因突变.(3)结直肠腺癌中,KRAS、BRAF及PIK3CA基因突变率分别为48％ (24/50)、6％ (3/50)及4％(2/50).结论 结直肠锯齿状病变与传统腺瘤在免疫表型及基因突变等方面存在着一定的差异,MMR与MGMT在“锯齿状肿瘤”癌变通路中起着重要的作用.KRAS基因突变是结直肠腺癌癌变过程中发生较早的重要遗传学改变.

abstractsObjective To analyze immunophenotypes and gene mutations of colorectal precancerous lesions and adenocarcinoma,and to compare the difference of carcinogenetic mechanisms between the two precancerous lesions.Methods Fifty-three cases of colorectal serrated lesions including 30 hyperplastic polyps,20 sessile serrated adenomas (SSA) and 3 mixed polyps were collected from January 2006 to June 2012.Forty-five cases of traditional adenomas and 50 cases of colorectal adenocarcinomas were also recruited.Thirty hyperplastic polyps,20 cases of SSA,3 mixed polyps and 45 traditional adenomas were investigated by immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins (MLH1,MSH2 and MSH6) and DNA methyltransferase MGMT.Mutations of KRAS,BRAF and PIK3CA genes in 10 cases of SSAs,10 traditional adenomas,1 mixed polyps and 50 colorectal adenocarcinomas were analyzed by PCR followed by direct Sanger sequencing.Results (1) Only 3 cases of hyperplastic polyps lost MLH1 expression,and none of SSAs or traditional adenomas showed loss of MLH1.The negative expression rates of MSH2,MSH6 and MGMT in hyperplastic polyps and SSA were significantly higher than those of traditional adenomas.(2) KRAS mutation was found in 5/10 cases of SSAs,5/10 traditional adenomas and l/1 mixed polyps.(3) Colorectal adenocarcinomas harbored the mutations of KRAS (48％,24/50),BRAF (6％,3/50) and PIK3CA (4％,2/50).Conclusions Immunophenotypic and gene mutation profiles are different between colorectal serrated lesion and traditional adenoma.Alterations of MMR and MGMT expression play important roles in the pathogenesis of "serrated neoplasm".KRAS mutation is a significant genetic change in the early phase of colorectal carcinogenesis.