胃粘膜肠化生组织YNZ22基因杂合缺失及p53基因突变、蛋白表达的研究

STUDY ON THE LOSS OF HETEROZYGOSITY AT YNZ22 GENE AND p53 GENE ALTERATION IN THE GASTRIC INTESTINAL METAPLASIA

为探讨YNZ2 2基因杂合缺失 (LOH)及 p5 3基因突变、蛋白表达在胃粘膜肠上皮化生中的作用 ,应用PCR RFLP、PCR SSCP及免疫组化技术检测了不同类型肠化生组织中YNZ2 2基因LOH、p5 3基因素 5～ 8外显子突变及其蛋白表达。结果显示 ,YNZ2 2LOH率为 19.4% (6 / 31) ,p5 3突变率为 2 9.8% (14/ 47) ,p5 3蛋白表达率为 10 .0 % (6 / 6 0 )。将肠化生分为Ⅰ、Ⅱ、Ⅲ型 ,发现Ⅲ型肠化生中 p5 3突变率及其蛋白阳性表达率分别为5 7.1% (8/ 14)和 2 7.8% (5 / 18) ,均显著高于Ⅰ (18 2 % )、Ⅱ型肠化生 (2 .4% ) (均P <0 .0 5 )。p5 3蛋白表达与 p5 3基因突变显著相关 (P <0 .0 5 ) ,YNZ2 2LOH与 p5 3突变及蛋白表达无显著相关性 (P >0 .0 5 )。提示 ,YNZ2 2基因LOH及 p5 3基因异常可能在胃粘膜肠化生的发生及其癌变中起一定作用 ,p5 3基因有可能成为胃癌早期诊断的分子指标。

To investigate the role of loss of heterozygosity (LOH) at YNZ22 gene and p53 mutation, protein expression in the gastric intestinal metaplasia (IM). LOH at YNZ22 gene and mutation of exons 5 to 8 of p53 gene as well as p53 protein expression were examined with PCR RFLP, PCR SSCP and immunohistochemical technique in the different types of IM. Results LOH at YNZ22 gene was detected in 6/31 cases (19.4%) and mutation for p53 protein was found in 14/47 cases (29.8%), and positive staining for p53 protein was in 6/60 cases (10.0%) . IM was classified into type Ⅰ,ⅡandⅢ. It was found that p53 gene mutation rate(57.1%,8/14)and its protein expression rate (27.8%, 5/18)in typeⅢIM were significanty higher than those (18.2%, 2.4%)in typeⅠand ⅡIM ( P <0.05). There was a significant correlation between p53 protein expression and p53 gene mutation (p<0.05),but there was no correlation between LOH of YNZ22 and p53 alteration. Conclusions These results suggest that LOH at YNZ22 gene and p53 gene alteration may play a role in the development and malignant transformation of IM. p53 gene may be a useful molecular target for early diagnosis of gastric carcinoma.