Yeast functional assay of the p53 gene status in 11 cell lines and 26 surgical specimens of human hepatocellular carcinoma

The structural abnormalities of the p53 gene have frequently been detected in hepatocellular carcinomas (HCCs). To ascertain whether or not functional inactivation of this gene also occurs in HCCs, the transactivation of p53 gene products in 11 HCC cell lines maintained in our laboratory and 26 HCC surgical specimens was examined by yeast functional assay (functional analy sis of separated alleles in yeast: FASAY), which determines the functional status of the individual p53 alleles. The p53 gene product was inactivated in 8 of 11 (72.7%) HCC cell lines and in 12 of 26 (46.2%) HCC surgical spec imens. The inactivation frequency of the gene was 37.5%, 36.4%, and 71.4% i n well, moderately, and poorly differentiated HCCs, respectively. In HCC su rgical specimens larger than 5 cm in diameter, the inactivation frequency w as 83.3% while in those smaller than 2.5 cm, it was 14.3%. These results sh ow that functional inactivation of p53 gene products often occurs in HCCs a nd that the inactivation frequency of the gene in HCCs is well correlated w ith differentiation degree and tumor size, suggesting that the inactivation of p53 gene products plays a role in progression from well to poorly diffe rentiated HCC.