LOSS OF THE TUMOR-SUPPRESSOR P53 GENE AT THE LIVER-CIRRHOSIS STAGE INJAPANESE PATIENTS WITH HEPATOCELLULAR-CARCINOMA

The incidence of p53 gene aberrations is reported to be about 20-50% i n hepatocellular carcinomas (HCCs). In most cases, HCC is clinically p receded by liver cirrhosis, but the genetic changes in cirrhosis are n ot known well. Therefore, we studied the loss of heterozygosity (LOH) of the p53 gene in cirrhotic and neoplastic foci in the livers of pati ents with HCC. To assess the relationship between the LOH status of th e p53 gene in the liver cirrhosis stage and that in HCC, we analyzed t he samples microdissected from paraffin-embedded tissues using the pol ymerase-chain-reaction-based assay. We studied 18 patients with HCC. F ourteen of the 18 cases showed constitutional heterozygosity for the m icrosatellite markers. In 8 (57%) of the 14 informative cases, LOH was detected in primary HCCs. Among these 8 doubly informative (informati ve and LOH positive in primary HCC) cases: 5 cases (63%) showed LOH in liver cirrhosis lesions. The pattern of p53 allelic loss in the cirrh otic foci was identical with that in the corresponding tumor. The rema ining 6 cases without LOH of the p53 gene in HCC showed no p53 loss in any cirrhotic foci. LOH of the p53 gene may occur before the developm ent of HCC.