肝细胞癌P53基因突变和蛋白表达的研究

为了阐明Ｐ５３肿瘤抑制基因突变在人肝细胞癌发生和发展中的作用。应用聚合酶链反应－单链构象多态性银染技术和ＤＮＡ直接测序法研究了肝细胞Ｐ５３基因的分子结构改变，结果表明：３１％的病例显示有Ｐ５３基因突变，低分化癌的突变率显著高于高／中分化癌的突变率，突变主要集中于外显子７和１上显子８。免疫组织化学染色表明：４２例肝细胞癌中２２例有Ｐ５３蛋白的核内堆积，低分化癌，ＨＢｓＡｇ阳性病例和伴有肝硬化患者的Ｐ

MUTATION OF P53 GENE AND EXPRESSION OF P53 PROTEIN IN HUMAN HEPATOCELLULAR CARCINOMA

The molecular structural changes of P53 was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and silver staining techniques,direct DNA sequencing in human hepatocellular carcinoma.P53 gene mutations were detected in 31%(13 out of 42) of cases.The mutation rate of P53 gene was obviously higher in poorly differentiated carcinoma than highly/moderately differentiated carcinoma(P<0.01).P53 gene mutation was frequent and clustered in exon 7 and 8.Nuclear accumulation of the P53 protein was observed in 22 out of 42 cases of hepatocellular carcinoma(51%) with immunohistochemical method.P53 protein expressions were obviously stronger in poorly differentialted carcinoma,HBsAg-positive cases,the patients who had concomitant liver cirrhosis than in highly/moderately differentiated carcinoma,HBsAg-negative cases,the patients who had not concomitant liver cirrhosis(P<0.05).In addition,there was a correlation between mutation and protein expression level.These data suggest that mutation of P53 gene,which result in abnormal protein accumulation,was a frequent molecular structural change and may have importance in tumor generation and progression in human hepatocellular carcinoma.