结肠腺癌组织hMLH1和hMSH2表达与FOLFOX方案辅助化疗疗效相关性分析

Correlation of expression of hMLH1 and hMSH2 proteins in colon adenocarcinoma with efficacy after adjuvant chemotherapy of FOLFOX regiment

目的:探讨Ⅲ期散发性结肠腺癌错配修复(mismatch repair,MMR)蛋白hMLH1、hMSH2表达状态与临床病理特征、FOLFOX方案辅助化疗疗效及预后关系。方法:收集2005-01-01-2007-12-31南通大学附属医院收治,临床及随访资料完整的散发性结肠癌根治术后Ⅲ期224例标本,免疫组化方法检测癌组织hMLH1和hMSH2蛋白的表达,分析MMR蛋白的表达与临床病理特征、FOLFOX方案辅助化疗疗效及预后的关系。结果:224例患者中,hMLH1蛋白表达缺失28例(12.5%),hMSH2蛋白表达缺失5例(2.2%),无2种蛋白同时表达缺失,2种蛋白表达缺失率合计为14.7%(33/224)。低分化癌组织中2种MMR蛋白的表达缺失率高于高中分化程度,P=0.046;右侧结肠癌2种MMR蛋白表达缺失率为23.2%(16/69),高于左侧结肠癌的11.0%(17/155),P=0.017。hMLH1和hMSH2蛋白表达状态与患者的年龄、性别和临床分期无关,P>0.05。MMR蛋白表达缺失与正常患者5年无病生存率(disease-free survival,DFS)分别为72.7%和54.5%,差异有统计学意义,P=0.047;MMR蛋白表达缺失患者5年总生存率(overall survival,OS)为78.8%,高于表达正常患者的65.4%,但差异无统计学意义,P>0.05。结论:hMLH1和hMSH2蛋白的表达状态有可能作为Ⅲ期散发性结肠腺癌FOLFOX方案辅助化疗疗效及预后预测的指标。

[-ABSTRACT] OBJECTIVE： To investigate the correlation of expression of mismatch repair （MMR） proteins （hMLH1 and hMSH2） in stage Ill sporadic colon adenocarcinoma with elinicopathologic feature,adjuvant ehemotherapic efficacy of FOLFOX regiment and prognosis. METHODS： The clinical and follow-up data were collected in 224 patients with stage Ⅲ sporadic colon adenocarcinoma and completely clinical and follow-up documents were collected. The patients were treated with radical colon resection from January 1st of 2005 to December 31st of 2007 in Affiliated Hospital of Nantong Universi- ty. The expression of hMLH1 and hMSH2 proteins in the samples of colon cancer were detected by immunohistochemical method. The relationships of the expression of hMLH1 and hMSH2 proteins with clinicopathologic factors,adjuvant che- motherapic efficacy of FOLFOX regiment and prognosis were analyzed. RESULTS： Among 224 cases 28 （12. 5 %） cases showed the lost of the hMLH1 proteins expression and 5 （2.2 %） cases showed lost of the hMSH2 proteins expression. There were no cases with lost of two proteins expression,and the total rate of lost expression was 14.7 % （33/214）. The rate of lost expression of the MMR proteins in poorly differentiated cancer was higher than the ones in moderately and well differentiated cancer （P=0. 046）. The rate of lost expression of the MMR proteins in right-sided colon cancer was 23.2% higher than the one in left-sided colon cancer which was 11.0% （P=0. 017）. The lost expression of the MMR pro- teins was not associated with the patient＇s gender, age and stages （P〉0.05）. The five years disease-free survival （DFS） in the patients of lost expression and normal expression of the MMR proteins were 72. 7% and 54. 5% respectively （P= 0. 047）,and the five years overall survival （OS） were 78.8% and 65.4% respectively （P〉0.05）. CONCLUSIONS： Thestatus of hMLH1 and hMSH2 proteins expression may be useful in the evaluation of adjuvant chemotherapic efficacy of FOLFOX regiment and prognosis for patients with stage Ⅲ sporadic colon adenoearcinoma after surgery.