Mutation of p53 and K-ras, and loss of heterozygosity of APC in intrahepatic cholangiocarcinoma

Lab Invest. 1999 Apr;79(4):477-83.


Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant tumor in liver; however, the carcinogenic mechanism of ICC is poorly understood. To analyze the molecular carcinogenesis of ICC, we examined the alterations of the p53, APC, and K-ras genes in 40 surgically resected ICC cases. The single-strand conformation polymorphism/sequencing revealed a p53 mutation in 12 cases (30%). An immunohistochemical overexpression of the p53 gene was detected in 10 cases (25%). The PCR/RFLP showed loss of heterozygosity of APC in 4 of 17 informative cases (23.5%). And the PCR/RFLP assay of K-ras codon 12 revealed the mutation in nine cases (22.5%). Twenty-one cases (52.5%) showed an alteration of at least one of the examined genes, and six (15%) carried an abnormality in more than two genes. The analysis of the clinicopathologic findings disclosed a significant relationship between the genetic alteration and gross type of the tumor: the p53 mutation was prominent in the ICC of mass-forming type, and K-ras mutation occurred more frequently in the ICC of periductal extension type (p < 0.05). These data suggest that each of the examined genes is involved in the development of ICC and that the p53 and K-ras mutation may play a role in the tumor growth pattern.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution
  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic*
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / pathology
  • Exons
  • Genes, APC*
  • Genes, p53*
  • Genes, ras*
  • Humans
  • Loss of Heterozygosity*
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational