Ⅱ～Ⅲ期结肠癌患者DNA错配修复状态与其临床特征及预后的关系

Relationship between DNA mismatch repair status and its clinical features and prognosis in patients with stage Ⅱ/Ⅲ colon cancer

目的分析Ⅱ~Ⅲ期结肠癌患者DNA错配修复(MMR)的状态与患者临床特征及预后的相关性。方法选取2007年1月至2010年6月我院肿瘤内科收治的308例行肿瘤根治术Ⅱ~Ⅲ期结肠癌患者的组织标本,以免疫组织化学法检测MLH1、MSH2、MSH6、PMS2的表达,将其结果分为MMR缺失(d MMR)组及MMR完整(p MMR)组,比较两组患者的临床特征及预后,并采用Cox比例风险模型分析MMR状态与结肠癌预后的相关性。结果本组结肠癌d MMR的发生率为20.8%(64/308),p MMR为79.2%(244/308)。d MMR组患者中,年龄≤60岁、Ⅱ期、低分化癌、近端结肠癌及含黏液分泌癌患者的比例较p MMR组显著增高,差异均有统计学意义(P<0.05)。d MMR组患者的复发转移率及病死率分别为18.8%(12/64)、12.5%(8/64),明显低于p MMR组的31.6%(77/244)、23.0%(56/244),差异均有统计学意义(P<0.05);d MMR组患者的5年无病生存率及5年总生存率分别为82.8%(53/64)、87.5%(56/64),明显高于p MMR组的69.3%(169/244)、77.0%(188/244),差异均有统计学意义(P<0.05)。经Cox比例风险模型分析结果提示,结肠癌MMR状态是影响患者无病生存时间及总生存时间的一个独立因素(P<0.05)。结论结肠癌不同MMR状态有着不同的临床特征,dMMR更多发生在年龄≤60岁、Ⅱ期、低分化癌、近端结肠癌及含黏液分泌癌的患者中,其可作为预测结肠癌预后较好的一个标志物。

Objective To analyze the relationship between DNA mismatch repair(MMR) and clinical features and prognosis in patients with stages Ⅱ/Ⅲ colon cancers. Methods The tissue specimen of 308 patients with stage Ⅱ/Ⅲ colon cancer who underwent radical tumor resection in Department of Medical Oncology in our hospital from January 2007 to June 2010 were selected. The expression of MLH1, MSH2, MSH6 and PMS2 were detected by immunohistochemistry, which were divided into defective MMR(d MMR) group and complete MMR(p MMR) group. The clinical features and prognosis between the two groups were compared. Cox proportional hazard model was used to analyze the relationship between MMR status and prognosis of colon cancer. Results The incidence of colon cancer d MMR was20.8%(64/308) in d MMR group, and 79.2%(244/308) in p MMR group. In d MMR group of patients, the proportion of patients within 60 years old, stage Ⅱ, poorly differentiated carcinoma, proximal colon and mucinous carcinoma were significantly increased compared with p MMR group(P<0.05). The recurrence rate and mortality rate of patients in d MMR group were 18.8%(12/64), 12.5%(8/64), respectively, which were significantly lower than those in p MMR group [31.6%(77/244), 23.0%(56/244), P<0.05]. The 5 year disease-free survival rate and overall survival rate in d MMR group were 82.8%(53/64), 87.5%(56/64), respectively, which were significantly higher than those in p MMR group [69.3%(169/244), 77.0%(188/244), P<0.05]. Cox proportional hazard model analysis showed that MMR status was an independent factor that affected the disease-free survival and overall survival time of patients(P<0.05).Conclusion Different MMR states of colon cancer have different clinical features, and d MMR is mostly occurred in patients within 60 years old, stage Ⅱ, poorly differentiated carcinoma, proximal colon and mucinous carcinoma. It can be used as a marker to predict the prognosis of colon cancer.