散发性结直肠癌中微卫星不稳定性及临床病理意义  

Microsatellite instability of sporadic colorectal carcinomas and its clinicopathological significance

作　　者：肖秀英[1] 周晓燕[1] 孙孟红[1] 颜歌[1] 杜祥[1] 

机构地区：[1]复旦大学附属肿瘤医院病理科复旦大学上海医学院肿瘤学系,上海200032

出　　处：《中华肿瘤杂志》2006年第4期289-293,共5页Chinese Journal of Oncology

基　　金：上海市科学技术发展基金资助项目(024119010)

摘　　要：目的通过微卫星位点BAT-25和BAT-26的分析,观察散发性结直肠癌原发和转移灶中微卫星不稳定性(MSI)的阳性率,并探讨其与临床病理参数的关系。方法收集73例结直肠癌原发灶和53例转移灶石蜡标本,分离基因组DNA,通过荧光标记多重PCR法扩增微卫星位点BAT-25和BAT-26;应用全自动DNA测序仪和GeneScan3.1软件进行片段分析,观察这2个位点重复序列长度的变化。以1例己知有MSI-H的遗传性非息肉病性结直肠癌(HNPCC)病例为阳性对照。结果73例散发性结直肠癌中,MSI的阳性率为15.1%,MSI与患者的性别、肿瘤发生部位、分化程度和预后有关(P<0.05);53例转移患者中,转移灶的MSI阳性率(17.0%)略高于原发灶(13.2%),差异无统计学意义(P>0.05),但有2例原发灶MSI阴性,转移灶MSI阳性。结论散发性大肠癌中MSI是一个常见的分子事件;MSI可作为临床判断大肠癌恶性程度、预后等的重要参考指标,根据MSI对散发性结直肠癌进行分类有重要的理论和实际意义;MSI在部分散发性大肠癌的转移中可能起一定的作用。Objective To investigate the incidence of mierosatellite instability （MSI） in sporadic colorectal carcinoma （CRC） using BAT-25 and BAT-26 loci, and its association with clinicopathological features. Methods Microsatellite analysis was performed on tissue samples from 73 primary and 53 metastatic tumors collected at the Department of Pathology, Fudan University Cancer Hospital in 2002. Genomic DNA was extracted from paraffin-embedded tissues. Microsatellite alterations of BAT-25 and BAT- 26 were detected using fluorescent PCR followed by fragment analysis on automatic DNA sequencer with GeneScan 3.1 software. A case of hereditary nonpolyposis colorectal cancer syndrome （ HNPCC ） with known high-frequency MSI （MSI-H） was included as positive control. Results Eleven out of 73 samples from primary tumors （15. 1% ） were MSI-positive and significandy associated with patient age, tumor site, differentiation and prognosis （ P 〈 0.05 ）. There was no significant difference between the positive rate of MSI in tissue samples from primary and metastatic sites among the 53 metastatic tumors, being 17.0% and 13.2%, respectively, P 〉 0. 05. Two cases with negative MSI at the primary site but positive at the metastatic sites were observed. Conclusion MSI is a frequent molecular event that may serve as a useful parameter for studying tumor biological behavior. MSI plays a partial role in the metastasis of sporadic CRC, but the role of mismatch repair genes and its exact mechanism remains to be determined. The classification of sporadic CRC according to MSI may be of importance both theoretically and practically.

关 键 词：结直肠肿瘤 微卫星不稳定性 肿瘤转移 

分 类 号：R735.3[医药卫生—肿瘤]