DNA错配修复基因hMLH1与hMSH2在结直肠癌合并慢性血吸虫肠病与散发型结直肠癌中表达的差异研究  

of DNA mismatch repair gene hMLH1 and hMSH2 between colorectal cancer and sporadic colorectal cancer

作　　者：陈寅波[1] 刘卓[1] 钱俊[1] 冯海洋[1] 李德川[1] 范永田[1] 

机构地区：[1]浙江省肿瘤医院结直肠肿瘤外科,杭州310022

出　　处：《中华胃肠外科杂志》2016年第1期75-79,共5页Chinese Journal of Gastrointestinal Surgery

摘　　要：目的研究DNA错配修复基因hMLH1和hMSH2在结直肠癌合并慢性血吸虫肠病患者与散发型结直肠癌患者的肿瘤组织中的表达差异。方法回顾性分析浙江省肿瘤医院2008年1月至2010年12月收治的338例结直肠癌患者的临床病理资料．根据术前患者病史和肿瘤标本病理检查结果，将患者分为慢性血吸虫肠病组（80例）和散发型结直肠癌组（258例）。应用免疫组织化学法检测hMLH1和hMSH2蛋白在两组患者肿瘤组织中的差异性表达．并分析其与患者临床病理特征的关系。结果与散发型结直肠癌组患者相比，慢性血吸虫病组患者的年龄更高[（62．2±9．6）岁比（57．2±11．7）岁，P=0．000]，术前血小板与白细胞水平更低[（197．0±59．6）×109／L比（217．0±84．3）×109/L，（5．9±1．9）×109/L（6．6±2．8）×109/L，均P=0．020]。两组患者的低分化和未分化肿瘤的比例分别为44．2％（34／77）和4．9％（12／247），差异具有统计学意义（P=0．001）。慢性血吸虫病组中hMLHl和hMSH2的表达水平均低于散发型结直肠癌组[77．5％（62／80）比98．1％（253／258），75．0％（60／80）比95．3％（246／258），均P=0．000]。合并慢性血吸虫病是hMLHl和hMSH2表达缺失的危险因素之一（RR：0．913，95％（7／：0．836～0．997，P=0．043），但非独立危险因素（RR：0．951，95％CI：0．867～1．043，P=0．286）。结论慢性血吸虫肠病的结直肠癌组织中hMLHl和hMSH2蛋白的表达水平低于散发型结直肠癌，提示慢性血吸虫肠病诱发结直肠癌的机制可能与hMLHl和hMSH2基因的缺失有关。Objective To investigate the expression difference of DNA mismatch repair gene hMLH1 and hMSH2 between schistosomiasis-associated cnlorectal cancer and sporadic colorectal cancer. Method Clinical and pathological data of colorectal cancer patients receiving operations in Zhejiang Cancer Hospital between January 2008 and December 2010 were retrospectively analyzed. Patients were divided into schistosomiasis group （n=80） and sporadic group （n=258） according to the preoperative history and pathologic results. Pathological specimens were collected and tissue chips were made to analyze the expression of hMLH1 and hMSH2 by immunohistochemistr. Results Compared with sporadic group, older age [ （62.2± 9.6） year vs. （57.2 ±11.7） year, P = 0.000）], lower platelet level [（197.0 ±59.6）×109/L vs. （217.0± 84.3） × 109/L, P = 0.02] and lower WBC level [（5.9± 1.9）×109/L vs. （6.6 ± 2.8） ×109/L, P = 0.02] were found in schistosomiasis group. Ratio of low differentiation-undifferentiation tumor was significantly higher in schistosomiasis group [44.2% （34/77） vs. 4.9% （12/247）, P〈0.05]. Lower positive rate of hMLH1 expression [77.5% （62/80） vs. 98.1% （253/258）, P = 0.000] and hMSH2 expression [75.0% （60/80） vs. 95.3% （246/258）, P = 0.000] was found in schistosomiasis group compared with sporadic group. Concurrent schistosomiasis was one of the risk factors of hMLH1/hMSH2 deficiency （RR： 0.913, 95% CI： 0.836-0.997, P = 0.043）, but not an independentfactor （RR： 0.951, 95%CI： 0.867-1.043, P=0.286）. Conclusion Schistosomiasis is associated with lower positive expression of hMLH1 and hMSH2, which indicates that hMLH1/hMSH2 deficiency may be a potential mechanism of schistosomiasis inducing carcinogenesis of colorectal cancer.

关 键 词：结直肠肿瘤 慢性血吸虫肠病 HMLH1 HMSH2 

分 类 号：R735.34[医药卫生—肿瘤]