Lynch综合征相关结直肠癌患者的初步筛查

Screening for Lynch syndrome in colorectal cancer

目的 探讨错配修复基因（MMR）蛋白的检测对Lynch综合征相关结直肠癌患者进行初步筛查的作用.方法 收集2012至2013年间100例连续的结直肠癌病例,采用免疫组织化学EnVision法检测MLH1、MSH2、MSH6和PMS2蛋白的表达,借助扩增阻滞突变系统（ARMS）方法检测MLH1蛋白失表达病例BRAF基因的突变状态.结果 免疫组织化学结果显示9％ （9/100）的病例出现MMR蛋白缺失表达,其中MLH1-/PMS2-和MSH2-/MSH6-者各3例,2例MLH6-,PMS2-者为1例,以MLH1和MSH2蛋白缺失表达为主.BRAF基因突变检测,证实1例患者存在突变,提示该患者可能存在因BRAF基因突变导致的MLH1基因甲基化,为散发性病例.MMR蛋白缺失表达患者发病年龄低于散发性结肠癌患者（P=0.011）,多发生于右半结肠（P=0.001）,组织形态学上常伴黏液腺癌分化（P=0.010）及肿瘤间淋巴细胞浸润.结论 对结直肠癌患者进行MMR蛋白的免疫组织化学染色,结合BRAF基因的突变检测,是初步筛查Lynch综合征的有效策略.

Objective To evaluate the application of mismatch repair （MMR） genes proteins expression to screen for Lynch syndrome in colorectal cancer patients.Methods One hundred consecutive colorectal cancers cases collected from 2012 to 2013 were tested immunohistochemically for the protein expression of MLH1,MSH2,MSH6 and PMS2,and also by the ARMS method for the mutation status of BRAF genes in those cases lacking protein expression for MLH1.Results The result of MMR immunocytochemistry showed that nine of 100 cases lacked MMR protein expression,including three cases each that were MLH1-/PMS2-and MSH2-/MSH6-respectively,two cases were MLH6-and one case was PMS2-; overall,the majority of these cases lacked protein expression of MLH1 and MSH2.The BRAF genes mutation test showed one case of mutation,indicating that the patient might have MLH1 gene methylation as a result of the mutation of BRAF genes,and that was a sporadic case.The age of onset for patients lacking MMR protein expression was lower than patients with sporadic colorectal cancer （P =0.011）.Colorectal cancers associated with the lack of MMR protein expression mostly occurred in the right colon （P =0.001）,and histomorphologically were often accompanied by mucinous adenocarcinoma （P =0.010） and tumor lymphocytic irnfiltration.Conclusion Immunohistochemical staining for MMR proteins in patients with colorectal cancer,accompanied by testing for BRAF genes mutation,may be an effective approach to screen for Lynch syndrome.