Analysis of K-ras codon 12 mutations and p53 overexpression in colorectal nodule-aggregating tumors

J Gastroenterol Hepatol. 2000 Oct;15(10):1151-7. doi: 10.1046/j.1440-1746.2000.02280.x.

Abstract

Background and aims: Morphologically, colorectal nodule-aggregating tumors are quite different from polypoid-type colorectal tumors that develop via the adenoma-carcinoma sequence. Although polypoid-type colorectal tumors are well known to have a high incidence of K-ras gene mutation and p53 overexpression, colorectal nodule-aggregating tumors have not been examined in terms of genetic changes and clinicopathological features. In the present study, therefore, we analysed the clinicopathological features, genetic changes in K-ras codon 12, and p53 overexpression in colorectal nodule-aggregating tumors.

Methods: A total of 18 colorectal nodule-aggregating tumors were surgically resected and then analysed clinicopathologically. Immunohistochemistry and polymerase chain reaction-single stranded conformational polymorphism were performed to analyse p53 abnormalities in the tumors. K-ras codon 12 mutations were screened out by the polymerase chain reaction-restriction fragment length polymorphism method and analysed by fluorescence direct sequencing.

Results: p53 overexpression was observed in six lesions (33%). p53-overexpressing cells were observed in parts of carcinoma or adenoma showing high-grade atypia. Four of the 10 (40%) samples had a p53 gene mutation. Nine of the 18 (50%) samples had a K-ras codon 12 point mutation. In eight cases (89%), the mutations of the K-ras codon 12 were of the same type: GGT (glycine) to GTT (valine).

Conclusions: The colorectal nodule-aggregating tumor has distinctive characteristics showing a morphological phenotype of the superficial-type tumors and genotype of the polypoid tumors in terms of K-ras gene mutation and p53 overexpression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics*
  • Adenoma / pathology*
  • Adenoma, Villous / genetics
  • Adenoma, Villous / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Carcinoma / genetics*
  • Carcinoma / pathology*
  • Cecum / pathology
  • Codon / genetics
  • Colon / pathology
  • Colon, Sigmoid / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • DNA, Neoplasm / genetics
  • Female
  • Genes, p53 / genetics*
  • Genes, ras / genetics*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Rectum / pathology

Substances

  • Codon
  • DNA, Neoplasm