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目的研究mdm2基因在原发性肝细胞癌(HCC)中的表达并探讨其与p53基因突变的关系.方法用银染PCRSSCP法检测p53基因第5~8外显子的突变,原位杂交检测mdm2基因mRNA的表达,SABC法检测mdm2蛋白的表达.结果393%(11/28)的病例有异常的电泳迁移率.p53基因突变与肿瘤的大小、分化及转移无关.原位杂交显示9例HCC出现mdm2基因mRNA增加,7例HCC可检测到mdm2蛋白表达,mdm2基因表达与HCC的大小、分化及是否转移无关.Ⅰ~Ⅱ级HCC中mdm2阳性表达率(133%)明显低于Ⅲ~Ⅳ级HCC中的阳性表达率(538%).11例有p53基因突变的HCC中,只有3例出现mdm2基因表达,另外6例有mdm2过表达的HCC未见p53基因突变.p53基因突变的HCC与p53基因无突变的HCC相比,mdm2基因表达阳性率无显著差别.结论p53基因突变和mdm2基因表达在原发性HCC的发病中起重要作用.mdm2基因表达与HCC的恶性程度相关.mdm2基因表达与p53基因是否突变无关.
Objective To investigate the expression of mdm2 gene in primary hepatocellular carcinoma (HCC) and explore its relationship with p53 gene mutation. Methods The mutation of exon 5-8 of p53 gene was detected by silver stain PCR-SSCP method. The mRNA expression of mdm2 gene was detected by in situ hybridization. The expression of mdm2 protein was detected by SABC method. Results 39.9% (11/28) cases had abnormal electrophoretic mobility. The p53 gene mutation was not associated with tumor size, differentiation and metastasis. In situ hybridization showed that mdm2 mRNA increased in 9 cases of HCC, and mdm2 protein was detected in 7 cases of HCC. The expression of mdm2 gene was not related to the size, differentiation and metastasis of HCC. The positive expression rate of mdm2 in I-II HCC (13. 3%) was significantly lower than that in III-IV HCC (53.8%). Of the 11 cases of HCC with p53 mutation, only 3 cases showed mdm2 gene expression. The other 6 cases with mdm2 overexpressed HCC had no p53 gene mutation. There was no significant difference in the positive rate of mdm2 gene expression between the HCC with p53 gene mutation and the p53 gene without mutation. Conclusion The p53 gene mutation and mdm2 gene expression play an important role in the pathogenesis of primary HCC. Mdm2 gene expression correlates with the degree of malignancy of HCC. The mdm2 gene expression was not related to mutation of p53 gene.