散发性多原发大肠癌微卫星不稳定研究

[目的]研究散发性多原发大肠癌微卫星不稳定发生频率,探讨其与异时多原发大肠癌的发生及散发性多原发大肠癌患者预后的关系。[方法]对上海肿瘤医院1985年～2000年病理资料完整的70例散发性多原发大肠癌患者的124个存档蜡块,以及随访3年以上的35例散发性单原发大肠癌患者的肿瘤组织进行微卫星不稳定测定。PCR法检测BAT25、BAT26两个位点来判断肿瘤组织微卫星不稳定情况,两个位点均阳性作为判断微卫星不稳定标准。微卫星不稳定结果与临床病理参数之间的比较采用χ2检验,生存分析采用Kaplan-Meier生存曲线、Log-Rank检验分析。P值<0.05作为差异有统计学意义的界限。[结果]散发性多原发大肠癌中,25.8%的肿瘤表现高度微卫星不稳定(MSI-H),单原发大肠癌为5.7%(25.8%vs.5.7%,P=0.01)。其中同时多原发大肠癌MSI阳性率为15.6%,异时多原发大肠癌为36.7%(15.6%vs.36.7%,P=0.007);40岁以下,阳性率为53.8%,40岁以上为22.5%(53.8%vs.22.5%,P=0.015);右结肠阳性率为41.2%,左结肠阳性率为15.1%(41.2%vs.15.1%,P=0.001);Dukes’A、B、C、D期阳性率分别为25.0%、33.3%、22.2%、11.1%(P>0.05);高、中、低分化腺癌及黏液腺癌分别为20.0%、25.9%、21.1%、31.6%(P>0.05)。70例患者平均随访61个月,MSI-H患者和MSS患者5年生存率分别为80.95%和57.14%(P<0.05)。[结论]MSI可以作为一个重要的独立的危险因素预测异时大肠癌的发生,亦可作为一个重要指标判断散发性多原发大肠癌患者的预后。

Telomerase activity in colorectal cancer,prognostic factor and implications in the microsatellite instability pathway

AIM： To determine whether the telomerase activity is related to the Microsatellite instability （MSI） genetic pathway and whether it means a difference in the survival.METHODS： The population consisted of 97 colorectal cancer patients. MSI determination was performed in accordance with the NCI criteria using PCR and Genescan. Telomerase activity was determined by the TRAP-assay, an ELISA procedure based on the amplification of telomeric repeat sequences.RESULTS： 6.2% showed high MSI （MSI-H）, 10.3% showed low MSI （MSI-L） and 83.5% did not show this alteration （MSS）. Positive telomerase activity was detected in 92.8% of the patients. 83.3% of MSI-H tumors showed positive telomerase against 93.8% of MSS tumors. In the overall survival analysis the absence of telomerase activity conferred a better prognosis.CONCLUSION： Previous works have shown that tumors which develop via the MSI pathway present a better prognosis. No link between telomerase activity and MSl status is observed, although sample sizes are small. Patients with telomerase negative tumors had better overall survival than patients with telomerase positive tumors.