胃癌组织p53基因缺失和异常表达

p53 GENE DELETION AND ABNORMAL EXPRESSION IN GASTREC CARCINOMA

检测２０例行胃癌根治手术患者的癌组织和对应的正常粘膜组织中ｐ５３基因ＤＮＡ结构和蛋白表达。Ｓｏｕｔｈｅｒｎ印迹显示３０％（６／２０）的胃癌组织中存在ｐ５３基因部分缺失。应用抗ｐ５３单克隆抗体－ＰＡｂ１８０１和ＡＢＣ免疫组织化学技术检测冰冻切片组织中ｐ５３蛋白的表达，结果表明，５５％（１１／２０）胃癌组织中存在突变ｐ５３蛋白高表达，阳性染色部位位于细胞核和／或细胞浆中，所有正常组织标本中均未见阳性染色，低分化腺癌ｐ５３阳性表达率显著高于分化好的胃癌（Ｐ＝０．０１１６），ｐ５３蛋白高表达和等位基因缺失密切相关（ｒ＝０．５９）。结果提示，在人类胃癌形成和肿瘤演进过程中，ｐ５３基因失活是一个重要的事件，ｐ５３基因结构和产物的变化可以作为新的肿瘤相关标志，这对判断胃癌生物学行为，识别具有高度恶化倾向的肿瘤，估价胃癌病员的预后和指导临床治疗有一定的作用。

Abstract We studied p53 gene at the DNA and protein level in human gastric cancer tissues and corre-sponding normal gastric mucosae from 20 cases of patients undergone radical surgery. BY South-ern blotting, the p53 gene was found tobe partially deleted in 30%(6/20) of gastric cancer tis-sues. ABC immunohistochemical study of p53 expression was carried out on cryostat sections us-ing monoclonalantibodies(PAb 1801)to p53. High level expression of mutated p53 protein wasdetected in 55%(11/20) gastric cancer tissues. The staining pattern was intranuclear and/or in-tracytoplamic. There was no detectable staining of any of the normal gastric tissues with 1801 an-tibody. The postive rate of p53 overexpression was higher in poorly-differenciated glandular car-cinomas than well-differenciated cancer(P=0.0116).Highly significant association exists be-tween high level p53 expression and allele deletion (r=0.59).The date indicate that inactivationof p53 gene is important inhuman gastric carcinogenesis and tumor progression.The assay of p53gene structure and products may provide new biologically relevant tumor marks for predicting thebehavior of gastric carcinomas , identifying more aggressive tumors ,determining prognosis of thepatients and guiding treatment.