EXPRESSION OF P53 GENE IN 184 UNIFOCAL HEPATOCELLULAR CARCINOMAS - ASSOCIATION WITH TUMOR-GROWTH AND INVASIVENESS

To elucidate the biological significance of the p53 gene expression in human hepatocellular carcinoma (HCC), the p53 protein was studied in 184 resected unifocal primary HCCs, including 102 small (less-than-or- equal-to 5 cm) and 82 large HCCs (>5 cm), using immunocytochemistry. T he p53 mRNA expression was analyzed in 69 cases using Northern hybridi zation. The p53 protein, which was detected in 58 HCCs (31.5%), was ov erexpressed more frequently in HCC with elevated serum alpha-fetoprote in level (37.9 versus 25%, P < 0.04), in large HCC (39.0 versus 25.5%, P < 0.03), and in invasive HCC (35.1 versus 13.3%, P < 0.01). The ove rexpression of p53 protein closely correlated with p53 mRNA overexpres sion (75 versus 44.4%, P < 0.003), and p53 gene mutation (76.9 versus 19.2%, P < 1 x 10(-9)). HCCs with p53 protein expression (group A) and those negative for both p53 protein and mRNA expression (group B) had an unfavorable outcome, while HCC with no p53 protein but with p53 mR NA overexpression (group C) had the best outcome; the 4-year survival was 26.1, 26.3, and 62.5%, respectively. The p53 gene mutation was sig nificantly higher in group A HCC (76.9%) than in groups B (27.3%) and C (23.5%), P < 0.0001. The results suggest that the p53 protein and mR NA expression patterns in HCC correlate with p53 gene mutation and tum or behavior and may serve as a molecular prognostic factor.