Absence of P53 Gene Mutations in Hepatocarcinomas from a Mediterranean Area of Spain. A Study of 129 Archival Tumour Samples

The incidence of p53 gene abnormalities in human hepatocellular carcinoma (HCC) varies in different geographical areas, being higher in regions where hepatitis virus infection and dietary exposure to aflatoxin B1 are the most common aetiological agents. These mutations are less frequently encountered in Europe, although some studies have reported p53 protein overexpression in up to 45% of cases analysed. We have analysed 129 tumour samples of primary malignant hepatic neoplasms recovered from paraffin blocks processed in two pathology laboratories in a Mediterranean area of Spain (Valencia and Gerona). Among 14 cases in which p53 immunohistochemistry expression proved positive, 5 stained in more than 50% of the cell nuclei. By PCR-SSCP analysis we could detect the complete sequence from exon 5 through 8 in 70 cases and part of this region in the remaining cases, but no mutations were found. We found no relationship with the clinical stage, tumour stage or clinical outcome. We conclude that p53 gene alterations are not a major event in the malignant transformation of hepatic cells in this region of the Mediterranean. The variable incidence of p53 gene alterations in other geographical areas may reflect a different genetic background for the aetiology of HCC.