摘要目的 探讨胃癌中细胞周期蛋白依赖性激酶抑制蛋白27基因(P27KiP1)蛋白表达、基因突变及启动子甲基化的关系.方法 采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶(SP)法、聚合酶链式反应-单链构象多态性分析(PCR-SSCP)技术、甲基化特异性聚合酶链式反应(MSP)方法分别检测97例胃癌中P27KiP1基因蛋白表达、基因突变及启动子甲基化,并选取25例正常胃黏膜组织作对照.结果 正常胃黏膜组织中P27KiP1蛋白高表达率明显高于胃癌组(x2=31.02,P＜0.01).早期胃癌组中P27KiP1蛋白高表达率也高于进展期胃癌组(x2=13.55,P＜0.01).正常胃黏膜组织中未检测到基因突变及启动子甲基化,胃癌组织中检测到P27KiP1基因突变及启动子甲基化,但在早期胃癌及进展期胃癌中两者差异无统计学意义(x2 =0.13、0.32,P＞0.05).46例P27KiP1蛋白高表达病例中仅有5例出现启动子甲基化,而在51例P27KiP1蛋白低表达病例中启动子甲基化高达21例,另有5例出现基因突变(x2=17.89,P ＜0.01).结论 P27KiP1蛋白的表达下调或缺失与胃癌的发生发展有关.P27KiP1基因突变及启动子甲基化在胃癌的早期阶段就可能已经发生并保存下来.P27KiP1基因启动子甲基化及基因突变,特别是启动子甲基化可以引起P27KiP1蛋白表达下调或缺失.

abstractsObjective To explore the relationship between the expression,mutation and promoter methylation of cyclin dependent kinase inhibitor protein 27 (P27KiP1) gene in gastric carcinoma.Methods Expression of P27KiP1 was investigated by using SP immunohistochemical staining,mutation was assayed by single-strand conformation polymorphism analysis (PCR-SSCP) and Promoter Methylation was assayed by methylation-specific PCR (MSP) in 97 cases of carcinoma,25 cases normal gastric tissues.Results The expression of P27KiP1 in normal gastric cases was higher than its in gastric carcinoma tissues (x2 =31.02,P ＜ 0.01).The expression of P27KiP1 in early gastric cases was also higher than its in advanced gastric carcinoma tissues (x2 =13.55,P ＜0.01).mutation and promoter methylation chould not be assayed in normal gastric tissues aud they were chould be assayed in carcinoma tissues,but there were no difference between early and advanced carcinoma tissues (x2 =0.13,0.32. P ＞ 0.05).There was a inverse association between expression of P27KiP1 and Promoter Methylation,mution (x2 =17.89,P ＜ 0.01).Conclusion The expression of P27KiP1 was associated with the occurrence and development of gastric carcinoma.P27KiP1 gene mutation and promoter methylation maybe occurred in early stage of this carcinoma and they might lead to the down or loss exprssion of P27KiP1 of gastric carcinoma.