Mutation of p53 and K-ras, and loss of heterozygosity of APC in intrahepatic cholangiocarcinoma.
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.
Kang
Y K
YK
Department of Pathology, Inje University Seoul Paik Hospital, Seoul National University College of Medicine, Korea.
Kim
W H
WH
Lee
H W
HW
Lee
H K
HK
Kim
Y I
YI
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D005091:Exons; D017491:Genes, APC; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational