APC, K-ras codon 12 mutations and p53 gene expression in carcinoma and adenoma of the gall-bladder suggest two genetic pathways in gall-bladder carcinogenesis

Takao Itoi, Hidenobu Watanabe, Yoichi Ajioka, Yasuhiro Oohashi, Kazuo Takei, Ken Nishikura, Yusuke Nakamura, Akira Horii, Toshihiko Saito

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Current histopathological evidence suggests that gall-bladder cancer has two main morphological pathways for its development: de novo (ab initio) origin and adenoma-carcinoma sequence. In order to investigate the genetic difference between them, APC mutations were examined by RNase protection analysis, K-ras mutations by nested polymerase chain reaction-restriction fragment length polymorphism analysis, and p53 gene overexpression by immunohistochemical analysis in both tumors and benign lesions of the gall- bladder. Overexpression of the p53 gene was detected in 105 of 164 (64%) de novo carcinomas regardless of size and depth of invasion, but not in 16 tumors of carcinoma-in-pyloric-gland-type adenoma, or in 51 adenomas (47 pyloric gland-type and 4 intestinal-type). K-ras codon 12 mutation was detected in 4 of 40 (10%) de novo carcinomas, all four being associated with p53 gene overexpression, but not in 12 tumors of carcinoma in adenoma or 16 adenomas (14 pyloric gland-type and 2 intestinal-type). APC mutation was not found in 16 de novo carcinomas or the one pyloric gland-type adenoma examined. These results suggest that there are two distinct genetic pathways in gall-bladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, and carcinoma-in-pyloric- gland-type adenoma develops from p53-, K-ras-, and APC-gene-unrelated, as yet unknown, alteration.

Original languageEnglish
Pages (from-to)333-340
Number of pages8
JournalPathology international
Volume46
Issue number5
DOIs
Publication statusPublished - 1996 Jan 1
Externally publishedYes

Keywords

  • APC
  • K-ras
  • gall-bladder carcinogenesis
  • p53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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