Overexpression of p53 in a large series of patients with hepatocellular carcinoma: a clinicopathological correlation.

p53 mutant protein has been found in a variety of human malignancies. In order to assess the controversial role of p53 protein in hepatocellular carcinoma (HCC) we studied its immunohistochemical expression in a series of 193 HCC specimens. Positive immunostaining for p53 was detected in the nuclei of neoplastic cells of 29 (15%) HCCs. There was no immunohistochemical evidence of mutant p53 expression either in normal or cirrhotic tissue surrounding neoplastic tissue. Higher alphafetoprotein serum levels were significantly associated with p53 overexpression. A prevalence of p53+ HCC specimens was seen in HCV negative patients (36% vs 13%, p < 0.05). No statistically significant correlations between p53 overexpression, age, sex, and HBV infection status were found. As regards histological grading, p53 was detected more frequently in tumours with poor cellular differentiation, although this finding does not reach statistical significance. The p53+ HCC rate was comparable to that attributed to the low incidence areas for HCC, in epidemiological studies. Moreover, p53 mutation seems to be related to the reactivation of alphafetoprotein gene to a more aggressive phenotype and to a later stage of liver carcinogenesis.