中国人遗传性非息肉病性结直肠癌错配修复缺陷表型分析  

Mismatch repair defective phenotype in hereditary nonpolyposis colorectal cancer in the Chinese

作　　者：蔡崎[1] 孙孟红[1] 陆洪芬[1] 徐晓丽[1] 闵大六[1] 张太明[1] 施达仁[1] 

机构地区：[1]复旦大学附属肿瘤医院病理科,上海200032

出　　处：《中华肿瘤杂志》2003年第5期420-424,共5页Chinese Journal of Oncology

基　　金：上海市医学重点发展基金资助项目 (肿瘤病理 ;993 0 2 5 )

摘　　要：目的　对中国人遗传性非息肉病性结直肠癌的肿瘤组织进行hMSH2 和hMLH1蛋白表达监测及微卫星不稳定性检测。方法　共收集 5 8个符合不同临床诊断标准的家系 ,对符合Amsterdam标准 2 4个家系 (AC组 )的 38个肿瘤 (来自 2 2个家系 )、符合日本标准 15个家系 (JC组 )的 16个肿瘤 (来自 12个家系 )、符合Bethesda指导纲要的 19例患者 (BG组 )中 12例的 13个肿瘤组织进行研究。选取 5个微卫星位点BAT2 6、BAT2 5、D2S12 3、D5S346和D17S2 5 0及单克隆抗体hMSH2 和hMLH1用于分析。结果　AC组家系 10 0 %表现为高度微卫星不稳定性 (MSI H) ,其中 81.8% (18/ 2 2 )表现为hMSH2 和hMLH1表达异常 ;JC组家系中 ,93.3% (14 / 15 )和 1/ 1个腺瘤表现为MSI H ,4 5 .5 % (5 / 11)表现为hMSH2 或hMLH1表达异常 ;BG组家系中 ,5 3.8% (7/ 13)患者肿瘤表现为MSI H ,其中 4 / 7表现hMSH1表达异常。结论　不同临床诊断标准的家系 ,其肿瘤组织MSI H阳性和错配修复蛋白表达异常的频率不同 ,Amsterdam标准和日本标准可较准确地反映肿瘤组织中错配修复缺陷情况 ,但Bethesda指导纲要也不可或缺。在临床诊断的基础上 ,合用免疫组化和微卫星不稳定性检测 ,可以较全面地检测到错配修复缺陷肿瘤。Objective To study the protein expression pattern of DNA mismatch repair genes hMSH_2 , hMLH_1 and the microsatellite instability (MSI) status in the tumor tissue from hereditary nonpolyposis colorectal cancer in the Chinese. Methods Fifty-eight families fulfilling different clinical criteria including Amsterdam Criteria (AC) (22/24 families, 38 tumors), Japanese Criteria (JC) (12/15 families, 16 tumors) and Bethesda Guidelines (BG) (12/19 patients, 13 tumors) were studied. Monoclonal antibodies against hMSH_2, hMLH_1 proteins and a panel of microsatellite markers (5 loci) including BAT26, BAT25, D2S123, D5S346 and D17S250 were used for study. Results MSI-H was identified in all 22(100%) AC tumors, with 81.8% (18/22) showing altered hMSH_2 or hMLH_1 expression; in 14/15(93.8%) JC cancer, 1/1(100%) JC adenoma, with 45.5% (5/11) showing altered hMSH_2 or hMLH_1 expression; and in 7/13 (53.8%) BG tumors, with 4/7 showing loss of hMSH_2 or hMLH_1 gene expression. Conclusion The frequency of MSI-H and loss of mismatch repair protein are different in the families fulfilling different clinical criteria. Amsterdam Criteria and Japanese Criteria are the two most useful criterion systems for identifying mismatched repair defective tumors. However, Bethesda Guidelines should also be used for detecting more such tumors. The combination of immunohistochemical methods and microsatellite instability analysis is an effective strategy to detect the mismatch repair defective tumors. A close correlation does exist between hMSH_2 , hMLH_1 protein expression pattern and MSI status.

关 键 词：中国人 遗传性非息肉病性结直肠癌 错配修复缺陷表型分析 病理 

分 类 号：R735.3[医药卫生—肿瘤]