K-ras基因状态及ras蛋白表达在胃印戒细胞癌免疫表型分类中的意义

摘要

Objective To investigate the significance of K-ras gene status and ras protein expression in immunophenotypic classification of gastric signet ring cell carcinoma.Methods The expression of ras protein in 180 cases of gastric signet-ring cell carcinoma was detected by tissue microarray immunohistochemistry.Meanwhile,the mutation in codon 12,13 of K-ras gene was determined by using PCR-based DNA direct sequencing analysis.Results The rate of ras protein expression was 27.8％.The rate of ras protein expression in intestinal phenotype was significantly higher than those in gastric and gastrointestinal phenotypes(P<0.05).The rate of ras protein expression in cases with lymph node metastasis was significantly higher than those in cases without nodal involvement(P<0.05).The rate of ras protein expression was significantly higher in cases with deeper invasion(P<0.05).The frequency of K-ras gene mutation was 22(12.2％).All of them were found in codon 12.The types of mutation included GGT→AGT(1 case),GGT→TGT(1 case),GGT→GCT(2 cases),GGT→GTT(8 cases)and GGT→GAT(10 cases).K-ras mutation was significantly associated with intestinal phenotype(P<0.05).The rates of ras protein expression in cases with mutational type of K-ras gene was higher than those in cases with wild type(P<0.05).The ras protein expression was positively associated with K-ras gene mutation(r=0.61,P<0.05).Conclusion The ras protein expression is correlated with nodal involvement and invasion.K-ras gene mutation and expression of ras protein is related to phenotypic classification,and they might influence the phenotypic transformation in gastric signet ring cell carcinoma.%目的 探讨K-ras基因状态及ras蛋白表达在胃印戒细胞癌免疫表型分类中的意义.方法 应用组织芯片免疫组织化学技术检测180例胃印戒细胞癌组织中ras蛋白的表达;PCR扩增和DNA直接测序法检测癌组织中K-ras基因12、13密码子的突变情况.结果 ras蛋白阳性50例(27.8％),ras蛋白阳性表达率在肠型印戒细胞癌中显著高于胃型和混合型印戒细胞癌(P<0.05).在淋巴结转移阳性组织中,ras蛋白阳性表达率明显高于无淋巴结转移组织(P<0.05);随着肿瘤侵袭、演进及临床分期的升高,ras蛋白阳性表达率明显增高(P<0.05).K-ras基因突变型22例(12.2％).所有突变位点均位于12密码子,突变类型包括:GGT→AGT 1例,GGT→TGT 1例,GGT→GCT 2例,GGT→GTT 8例,GGT→GAT 10例.13密码子未发现突变.肠型印戒细胞癌K-ras基因突变率显著高于胃型和混合型印戒细胞癌(P<0.05).K-ras基因突变型病例ras蛋白阳性表达率明显高于K-ras基因野生型病例(P<0.05).Spearman等级相关分析显示,ras蛋白表达与K-ras基因突变呈正相关(r=0.61,P<0.05).结论 ras蛋白的过表达可能与胃印戒细胞癌侵袭潜能、淋巴结转移相关,ras蛋白表达和K-ras基因突变与肿瘤的免疫表型变化存在相关性,它们在癌细胞表型转化过程中可能起到一定作用.