微卫星不稳定在散发性Ⅱ、Ⅲ期直肠癌中的意义

Significance of microsatellite instability in sporadic stage Ⅱ and Ⅲ rectal cancer

目的探讨微卫星不稳定(MSI)状态与散发性Ⅱ、Ⅲ期直肠癌临床病理特征和预后的关系。方法选取128例散发性Ⅱ、Ⅲ期直肠癌患者的手术切除标本和相应的正常组织,采用Bethesda标记通过PCR扩增和变性凝胶电泳-银染法检测微卫星状态,分析其与临床病理特征和预后的关系。结果 12例肿瘤为高频率MSI(MSI-H),28例肿瘤为低频率MSI(MSI-L),其余88例肿瘤为微卫星稳定(MSS)。与MSI-L和MSS肿瘤相比,大多数MSI-H肿瘤患者为女性(P=0.031)、黏液腺癌(P=0.023)、高分级(P=0.002)和术前血癌胚抗原(CEA)水平高(P=0.005)。单因素分析显示年龄、肿瘤分期、组织学类型、分化程度和术前血CEA水平为总体生存的影响因素。多因素分析显示性别、年龄、肿瘤分期、组织学类型和术前血CEA水平为术后总体生存的独立影响因素。MSI-H肿瘤患者预后好于MSI-L/MSS肿瘤患者,但差异无统计学意义(P=0.986)。将Ⅱ期和Ⅲ期直肠癌患者分开分析,也未见MSI-H肿瘤患者预后明显优于MSI-L/MSS肿瘤(P=0.705和P=0.664)。结论散发性Ⅱ、Ⅲ期直肠癌患者,具有较高的MSI-H发生率,MSI不是一个预后因素,肿瘤分期比MSI状态更适合用于预测该类患者的预后。

Objective To investigate the relationship between microsatellite instability（MSI） status and clinicopathological features and prognosis in sporadic stage Ⅱ and Ⅲ rectal cancer patients.Methods The paired samples of tumors and corresponding normal tissue from 128 stage Ⅱ and Ⅲ rectal cancer patients were analyzed for MSI status using Bethesda markers by PCR amplification and denaturing 6% polyacrylamide gel containing 8M urea and silver-staining.The relationship between MSI status and clinicopathological features and prognosis was assessed.Results Twelve（9.3%） tumors demonstrated high-frequency microsatellite instability（MSI-H）,28（21.9%） were low-frequency MSI（MSI-L） and 88（68.8%） were microsatellite stable（MSS）.Compared with MSI-L and MSS tumors,most of the MSI-H tumors were female gender（P=0.031）,mucinous histology（P=0.023）,high grade of differentiation（P=0.002） and high level of preoperative serum CEA（P=0.005）.In the univariate analysis,age at diagnosis,stage,histology,grade of differentiation,preoperative level of CEA were significantly associated with higher survival.In the multivariate analysis,sex,age at diagnosis,tumor stage,histology and CEA were found to be significantly and independently associated with survival.Rectal cancer patients with MSI-H did not show a better clinical outcome than that with MSI-L/MSS in all cases（P=0.986）,as well as in stage Ⅱ and stage Ⅲ disease analyzed separately（P=0.705 and P=0.664,respectively）.Conclusion There is a high incidence of MSI-H and MSI is not a prognostic factor in sporadic stage Ⅱ and Ⅲ rectal cancer in this study.Tumor stage is more suitable than MSI status for prediction of individual survival in sporadic stage Ⅱ and Ⅲ rectal cancer patients.