title: p53 expression in patients with cirrhosis with and without hepatocellular carcinoma.
abstract: BACKGROUND
  Mutated p53 acts as a dominant oncogene, whereas the wild type (wt) p53 gene product suppresses cell growth. Abnormalities in the p53 gene are reported in more than 50% of malignant tumors. Recently, an allelic loss of chromosome 17p, where the p53 gene is located, was found to be more frequent in hepatocellular carcinoma (HCC) cell lines and human tumors. In addition, in half of the cases of HCC from endemic areas for hepatitis B virus and aflatoxin, a hot spot point mutation at codon 249 was detected, as previously reported. Missense mutations in p53, mdm-2 complex formation, and other unknown mechanisms may lead to stabilization of the gene product, thus rendering it detectable by immunohistochemistry.
  
  
  METHODS
  To assess the relationship between p53 status at a premalignant stage and in HCC, the authors studied the immunohistologic expression of p53 in HCC and in the adjacent nontumorous resected liver tissue, using monoclonal antibody to wt and mutated p53.
  
  
  RESULTS
  Twelve of the 14 patients with liver tumors had HCC. Of the 12 patients with HCC and underlying cirrhosis, 8 (67%) had increased p53 expression in HCC cells. Eight of the 12 patients with p53-positive HCC cells had p53 overexpression in the nontumorous hepatocytes within regenerative nodules adjacent to HCC tissue. Three of 21 cirrhotic livers without a detectable tumor had increased p53 expression in the regenerative nodules. None of the 12 patients with chronic active hepatitis without cirrhosis or the 13 with a normal liver histology had increased p53 expression.
  
  
  CONCLUSIONS
  p53 overexpression in some cirrhotic livers and in nontumorous livers of patients with HCC may indicate a normal p53 gene response to cellular stress or, alternatively, to an abnormally or mutated p53 gene, and could occur before the development of HCC.
authors.affiliation: Department of Pathology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Livni
authors.forename: A
authors.initials: A
authors.lastname: Eid
authors.forename: Y
authors.initials: Y
authors.lastname: Ilan
authors.forename: A
authors.initials: A
authors.lastname: Rivkind
authors.forename: E
authors.initials: E
authors.lastname: Rosenmann
authors.forename: L M
authors.initials: LM
authors.lastname: Blendis
authors.forename: D
authors.initials: D
authors.lastname: Shouval
authors.forename: E
authors.initials: E
authors.lastname: Galun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D006521:Hepatitis, Chronic / Q000150:complications / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications* / Q000235:genetics*; D008113:Liver Neoplasms / Q000150:complications* / Q000235:genetics*; D008115:Liver Regeneration / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics