DNA错配修复蛋白缺失与Ⅱ、Ⅲ期结肠癌根治术后复发转移、预后的关系研究

Study on the Relationship between the Deletion of DNA Mismatch Repair Protein and the Recurrence,Metastasis and Prognosis after Radical Resection of StageⅡandⅢColon Cancer

目的探讨DNA错配修复蛋白(MMR)缺失与Ⅱ、Ⅲ期结肠癌根治术后复发转移及预后的关系。方法收集294例行结肠癌根治术的患者临床资料。采用免疫组织化学法检测患者手术切除标本MMR表达情况,统计分析MMR表达与患者临床病理参数的关系及对患者预后的影响。结果MMR表达状态与患者肿瘤部位、分化程度、分期相关(P<0.05)。但与患者性别、年龄、手术切除淋巴结数量、治疗模式、化疗周期无关(P>0.05)。多因素分析结果发现,肿瘤部位、分化程度、分期是影响MMR表达状态的独立性危险因素(P<0.05)。单因素分析结果显示:年龄、分化程度、T分期、N分期是影响患者复发转移率、总体生存率的危险因素。MMR状态与患者总体生存率相关,但与复发转移率无关。多因素分析结果显示,仅有N分期是影响患者复发转移率的独立性危险因素。仅有肿瘤分化程度、N分期、MMR状态是影响患者总体生存率的独立性危险因素。至随访截止日期,220例pMMR患者中,69例出现复发转移(31.4%),48例死亡(21.8%)。74例dMMR患者中,13例出现复发转移(17.6%),9例死亡(12.2%)。两组患者的无病生存率(χ^(2)=2.986,P=0.084)、总体生存率差(χ^(2)=3.934,P=0.047),差异均显著统计学意义。结论肿瘤部位、分化程度、分期与MMR表达状态密切相关。MMR表达缺失患者预后明显较差,可作为判断患者预后的一个潜在标志物。

Objective To investigate the relationship between the expression of DNA mismatch repair protein(MMR)and recurrence,metastasis and prognosis after radical resection of stage II and III colon cancer.Methods The clinical data of 294 patients undergoing radical resection of colon cancer were collected.The expression of MMR in the resected specimens was detected by immunohistochemistry,and the relationship between the expression of MMR and the clinicopathological parameters of the patients and the prognosis of the patients were analyzed statistically.Results The expression of MMR was correlated with tumor location,degree of differentiation and stage(P<0.05).However,there was no correlation with gender,age,number of lymph nodes removed,treatment mode and chemotherapy cycle(P>0.05).Multivariate analysis showed that tumor location,degree of differentiation and stage were independent risk factors affecting MMR expression(P<0.05).Univariate analysis showed that age,degree of differentiation,T stage and N stage were the risk factors affecting the recurrence and metastasis rate and overall survival rate of patients.MMR status was associated with overall survival,but not with recurrence and metastasis.Multivariate analysis showed that only N stage was an independent risk factor for recurrence and metastasis.Only the degree of tumor differentiation,N stage and MMR status were independent risk factors for overall survival.By the end of follow-up,there were 69 recurrences and metastases among 220 pMMR patients(31.4%),and 48 deaths(21.8%).Among 74 dMMR patients,there were 13 recurrences and metastases(17.6%),and 9 deaths(12.2%).The difference in disease-free survival rate(χ^(2)=2.986,P=0.084)and overall survival rate(χ^(2)=3.934,P=0.047)of patients in the two groups was statistically significant.Conclusion Tumor location,degree of differentiation and stage are closely related to MMR expression status.The prognosis of patients with lack of MMR expression is significantly worse,which can be used as a potential marker for judging the prognosis of patients.