检测微卫星不稳在中国遗传性非息肉病性结直肠癌患者诊断中的应用

Evaluation of microsatellite instability for detection of Chinese hereditary nonpolyposis colorectal cancer patients

背景与目的:遗传性非息肉病性结直肠癌(hered itary nonpolyposis colorectal cancer,HNPCC)是常染色体显性遗传综合征,国外报道90%的HNPCC肿瘤表现为微卫星不稳(m icrosatellite instab ility,MSI),可作为筛查HNPCC的金标准。本研究旨在了解中国HNPCC肿瘤MSI发生率以及可疑HNPCC患者大肠癌肿瘤中的MSI发生率,由此探讨大肠癌患者家族中的胃癌等HNPCC相关肿瘤对发现HNPCC患者的意义。方法:选择符合Am sterdam标准的HNPCC组大肠癌标本18例,和不符合Am sterdam标准、但高度怀疑为HNPCC的可疑HNPCC组大肠癌标本16例,检测BAT26、D2S123、BAX、IGFIIR、hMSH3和hMSH6 6个微卫星位点的微卫星不稳在两组中的发生率,比较两组微卫星不稳频率的差异。结果:上述各微卫星位点在HNPCC组和可疑HNPCC组标本中均显示较高的突变率。高度微卫星不稳肿瘤在两组标本中的检出率分别为94.4%和93.7%,差异无显著性。BAT26对高度微卫星不稳肿瘤敏感度高。结论:MSI在中国HNPCC患者中的发生频率与国外类同。仅用BAT26可发现大部分高度微卫星不稳肿瘤。将胃癌等HNPCC相关肿瘤纳入临床诊断标准,可能有助于避免在中国大肠癌人群中漏诊HNPCC患者。

Background and purpose： Hereditat7 nonpolyposis colorectal cancer is an autosomal dominant hereditary. cancer syndrome. 90% HNPCC tmnors have mierosatellite instability aceording to HNPCC literatures. This study was made to evaluate the frequency of microsatellite instability in Chinese HNPCC patients and suspected HNPCC patients. In addition, we discussed the detection of HNPCC in extraeolonic cancers, especially gastric cancer. Methods： Mierosatellite analysis was performed on 18 HNPCC patients who met Amsterdam criteria and 16 suspected HNPCC patients. Six microsatellite loci including BAT26, D2S123, BAX, IGFI1R, hMSH3 and hMSH6 were used. The frequency of MSI was compared between these two groups. Results： High-frequeney of MSI was demonstrated with 94.4% and 93.7% respectively in both of these two groups. Conclusions： The frequency of MSI in Chinese HNPCC patients was similar as reported in other countries. BAT26 alone could be used to detect most of the MSI tumors. It is helpful in order to avoid the misdiagnosis of HNPCC patients who has not fulfilled the Amsterdam criteria if extraeolonie cancers like gastric cancer are adapted into clinical criteria for HNPCC.