散发性多原发大肠癌微卫星不稳定研究

Microsatellite Instability in Sporadic Multiple Primary Colorectal Carcinoma

[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。

[Purpose] To investigate the frequency of mierosatellite instability （MSI） in sporadic multiple primary colorectal carcinomas （MCRC） and to assess the relationship between MSI and the prognosis of sporadic MCRC or the occurrence of metachronous MCRC. [Methods] From 1985 to 2000, 124 paraffin-embedded specimens from 70 sporadic MCRC patients with data integrity and 35 specimens from sporadic single colorectal cancer patients followed up over 3 years were available to determine MSI.DNA of these specimens was examined for two microsatellite marks （BAT25 and BAT26）.Microsatellite instability phenotype was defined as alterations in both loci. MSI and clinicopathologic parameters were compared by X^2 test. [Results] In sporadic MCRC, 32 carcinomas（25.8%） in 21 patients（30.0%） showed MSI-H. While only 2 carcinomas showed MSI-H（5.7%） in sporadic single colorectal carcinomas（25.8% vs. 5.7%, P=-0.01）. MSI-H was detected with higher frequency in metachronous carcinomas than that in synchronous carcinomas（36.7% vs. 15.6%, P=0.007）. Positive rate in young patients less than 40 years old was higher than that in more than 40 years old （53.8% vs. 22.5%, P= 0.015）, and that in right-sided colon was higher than that in left sided colon（41.2% vs. 15.1%, P=0.001）. The positive rates of MSI-H in Dukes＇A, B, C and D were 25.0%, 33.3%, 22.2% and 11.1% respectively（P〉0.05 ）. The positive rate of MSI-H in high differentiation adenocarcinomas was 20.0%, 25.9% in moderate differentia- tion adenocarcinomas, 21.1% in low differentiation adenocarcinomas, 31.6% inmucinous adenocarcinomas（P〉 0.05）. Mean follow-up period was 61 months（range 6～209, median 46）. [Conclusions] MSI may be regarded as an independent and important risk factor for predicting occurrence of metachronous of MCRC. MSI may be suitable as a marker for predicting the prognosis of sporadic MCRC.