ras Gene mutations and expression of Ras signal transduction mediators in gastric adenocarcinomas

Arch Pathol Lab Med. 2002 Sep;126(9):1096-100. doi: 10.1043/0003-9985(2002)126<1096:RGMAEO>2.0.CO;2.

Abstract

Objective: To investigate ras gene alteration in human gastric adenocarcinomas and its potential relationship to ras signal transduction mediators.

Design: Genomic DNA from 104 gastric tumors were analyzed by sequencing of polymerase chain reaction-amplified products for the presence of ras mutations. All the samples were further investigated with the use of immunohistochemical analysis for ERK1 and ERK2.

Setting: Tertiary care teaching hospital.

Patients: Seventy patients from a Korean population and 34 from a Midwestern US population composed of white Americans and African Americans.

Results: Fifteen tumors (14%) were positive for either H-ras or K-ras mutation: 9 (13%) of 70 Korean patients and 6 (18%) of 34 US patients. Seven (78%) of the 9 mutated tumors from Korean patients and all 6 (100%) from the US patients were intestinal-type lesions. Either ERK1 and/or ERK2 was overexpressed in 68 samples (65%). No association was established between ras mutations and overexpression of ERK1/2. However, the correlation between ERK1/2 and progression (early vs late) was statistically significant (P =.007).

Conclusions: These data suggest that ras mutations are uncommon in gastric adenocarcinomas and that differing racial and/or geographic mechanisms may not underlie ras gene alteration. Most ras mutations were, however, observed in the group of intestinal-type samples, supporting the different genetic mechanisms of carcinogenesis between the intestinal- and diffuse-type tumors. It is noteworthy that enhanced ERK1/2 activity could be one of the characteristics of tumor invasiveness in gastric cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • DNA Mutational Analysis
  • DNA, Neoplasm / analysis
  • Genes, ras*
  • Genetic Predisposition to Disease
  • Humans
  • Immunoenzyme Techniques
  • Korea
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Oligonucleotides, Antisense
  • Point Mutation*
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • United States

Substances

  • DNA, Neoplasm
  • Oligonucleotides, Antisense
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)