P53 EXPRESSION IN PATIENTS WITH CIRRHOSIS WITH AND WITHOUT HEPATOCELLULAR-CARCINOMA

Background. Mutated p53 acts as a dominant oncogene, whereas the wild type (wt) p53 gene product suppresses cell growth. Abnormalities in th e p53 gene are reported in more than 50% of malignant tumors. Recently , an allelic loss of chromosome 17p, where the p53 gene is located, wa s found to be more frequent in hepatocellular carcinoma (HCC) cell lin es and human tumors. In addition, in half of the cases of HCC from end emic areas for hepatitis B virus and aflatoxin, a hot spot point mutat ion at codon 249 was detected, as previously reported. Missense mutati ons in p53, mdm-2 complex formation, and other unknown mechanisms may lead to stabilization of the gene product, thus rendering it detectabl e by immunohistochemistry. Methods. To assess the relationship between p53 status at a premalignant stage and in HCC, the authors studied th e immunohistologic expression of p53 in HCC and in the adjacent nontum orous resected liver tissue, using monoclonal antibody to wt and mutat ed p53. Results. Twelve of the 14 patients with liver tumors had HCC. Of the 12 patients with HCC and underlying cirrhosis, 8 (67%) had incr eased p53 expression in HCC cells. Eight of the 12 patients with p53-p ositive HCC cells had p53 overexpression in the nontumorous hepatocyte s within regenerative nodules adjacent to HCC tissue. Three of 21 cirr hotic livers without a detectable tumor had increased p53 expression i n the regenerative nodules. None of the 12 patients with chronic activ e hepatitis without cirrhosis or the 13 with a normal liver histology had increased p53 expression. Conclusion. p53 overexpression in some c irrhotic livers and in nontumorous livers of patients with HCC may ind icate a normal p53 gene response to cellular stress or, alternatively, to an abnormally or mutated p53 gene, and could occur before the deve lopment of HCC.