【摘要】 目的探讨散发性大肠癌(Sporadic Colorectal Carcinoma,SCC)组织中脆性组氨酸三联体基因(Fragile Histidine Triad,FHIT)与错配修复基因(human DNA Mismatch Repair gene,hMMR)蛋白的表达之间有无相关性,以进一步研究大肠癌的发病机制。方法采用免疫组织化学的方法,检测了50例散发性大肠癌组织中的FHIT、hMLH1、hMSH2蛋白表达。结果(1)所有正常/非瘤组织中FHIT、hMLH1和hMSH2蛋白均为阳性表达。(2)FHIT蛋白表达的缺失癌在高、中和低分化癌中分别为3/10、11/29和9/11,低分化癌中FHIT表达的缺失癌与高、中分化癌比较,差异有显著性(P<0.01)。FHIT蛋白低表达癌在不同Duke’s分期癌中的分布为A和B期癌中总共为12/36,Duke’sC期癌中为11/14。已伴淋巴结转移的C期癌与未转移组的A和B期癌比较,差异有显著性(P<0.01)。(3)散发性大肠癌中主要发生突变的错配修复基因是hMLH1。hMLH1和(或)hMSH2蛋白低表达癌在高、中和低分化癌中分别为2/10、6/29和7/11,低分化癌中hMLH1或hMSH2蛋白表达的缺失与高、中分化癌比较,差异有显著性(P<0.05)。hMLH1和(或)hMSH2蛋白低表达癌在左侧和右侧大肠癌组织中分别为8/38和7/12,hMSH2蛋白低表达癌多分布在右侧大肠癌。(4)FHIT与MMR蛋白表达缺失之间具有很好的一致性(P<0.01)。结论在散发性大肠癌中FHIT蛋白表达的缺失与MMR基因表达的缺失有相关性。抑癌基因FHIT的异常改变可能是由于错配修复功能的缺陷造成的。更多还原

【Abstract】 Objective: To examined the FHIT and MMR gene proteins in Sporadic Colorectal Carcinoma tissues and to find whether the one is associated with the other. Methods: The expressions of FHIT、hMLH1、hMSH2 were detected by immunohisto-chemical staining in human tissues, including 49 cases of adenocarcinomas and 1 case of Signet ring cell carcinoma. Results: (1)All the normal/non-neoplastic tissues showed positive expression of FHIT, hMLH1 and hMSH2 protein. (2)In the 23 cases of reduced or absent FHIT expression, there were 3/10 in the well-differentiated cases, 11/29 in the moderately-differentiated cases and 9/11 in the poorly-differentiated cases. The incidence of reduced FHIT expression in Colorectal carcinomas was significantly higher in the poorly-differentiated cases than in the well-differentiated and moderately-differentiated cases(P<0.01) ,there were 12/ 36 in Duke’s A and B stage cases and 11/14 in Duke’s C stage cases; Reduced or absent FHIT expression in Duke’s,C stage cases which were companied by lymph node metastasis was significantly higher than in Duke’s A and B stage cases(P<0.01). (3)The MMR gene that mutated in sporadic colorectal cancer is mainly hMLH1 gene, which may be caused by hypermethylation of hMLH1 promoter. hMLH1 and (or) hMSH2 expression was noted in 2 of 10 well-differentiated cases, and in 6 of 29 moderately- differentiated cases, and in 7 of 11 poorly- differentiated cases. The ratio of the Reduced hMLH1 and (or) hMSH2 expression is significantly higher in the poorly-differentiated cases than in the well-differentiated and moderately- differentiated cases. In addition, reduced hML- H1 and (or) hMSH2 expression was observed in 7of 12 right-sided CRCs, and 8 of 38 left-sided CRCs. Loss of hMLH1 and (or) hMSH2 expressions was more frequently associated with right-sided location(P<0.05).(4)Reduced or loss FHIT expression was consistent with reduced hMLH1 and hMSH2 expression(P<0.01). Conclusion: The loss of expression of FHIT protein was significantly correlated with loss of MMR protein expression. The abnormal alteration of the suppressor gene FHIT could be caused by defective DNA mismatch repair function in human colorectal carcinoma.更多还原