Amplification of c-myc in hepatocellular carcinoma: correlation with clinicopathologic features, proliferative activity and p53 overexpression

Oncology. 1999;57(2):157-63. doi: 10.1159/000012024.

Abstract

Expression of the proto-oncogene c-myc has been implicated in liver regeneration and hepatocarcinogenesis. The biologic significance of c-myc gene amplification in human hepatocellular carcinoma, however, is unconfirmed. We correlated c-myc gene amplification with clinicopathologic features, proliferative activity, and p53 expression in 42 resected tumors. c-myc amplification in tumor tissue was determined using a differential polymerase chain reaction, a useful procedure for the evaluation of gene amplification in archival formalin-fixed paraffin-embedded tissues, in comparison with a dopamine D2 receptor gene. Proliferative activity was estimated by numbers of argyrophilic nucleolar organizer regions and immunohistochemical nuclear labeling rates using a monoclonal antibody against Ki-67. The c-myc gene was amplified in 14 of 42 tumors (33.3%). Amplification of c-myc was more frequent in younger patients and in larger tumors, and less differentiated tumors. No correlation was noted with alpha-fetoprotein level or viral hepatitis state. The amplification showed positive correlation with both proliferative activity and p53 overexpression. Disease-free survival in patients showing c-myc amplification was significantly shorter than in those without amplification. These results suggest that c-myc amplification is an indicator of malignant potential and poor prognosis in hepatocellular carcinoma. c-myc amplification and p53 alteration may be coparticipating events in the progression of these tumors.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / chemistry
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Division
  • DNA Primers
  • DNA, Neoplasm / genetics
  • Female
  • Gene Amplification*
  • Gene Expression Regulation, Neoplastic*
  • Genes, myc / genetics*
  • Humans
  • Liver Neoplasms / chemistry
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction / methods
  • Prognosis
  • Survival Analysis
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • DNA Primers
  • DNA, Neoplasm
  • Tumor Suppressor Protein p53