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Epidermal growth factor receptor (EGFR) status and K-Ras mutations in colorectal cancer

G Milano1, M-C Etienne-Grimaldi, L Dahan

  • 1Oncopharmacology Unit, EA3836, Centre Antoine-Lacassagne, Nice, France. gerard.milano@nice.fnclcc.fr

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|July 18, 2008
PubMed
Abstract

Insights

K-Ras mutations do not influence epidermal growth factor receptor (EGFR) status in colorectal tumors. This finding indicates that EGFR testing is independent of K-Ras mutation analysis for predicting treatment response in colorectal cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • K-Ras somatic mutations are known predictors of resistance to monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) in advanced colorectal cancer.
  • The relationship between K-Ras mutations and the overall status of EGFR in tumors has not been previously investigated.

Purpose of the Study:

  • To investigate the association between K-Ras mutations and EGFR tumoral status.
  • To analyze EGFR status by examining germinal polymorphisms, gene copy number, and gene expression in relation to K-Ras mutations.

Main Methods:

  • Analysis of 80 colorectal tumors (stage 0-IV) and 39 normal mucosas.
  • Detection of K-Ras mutations (codons 12 and 13) using PCR-RFLP assay.
  • Assessment of EGFR gene polymorphisms, gene copy number (PCR amplification), and EGFR expression (Scatchard binding assay).

Main Results:

  • No significant differences in EGFR high-affinity sites, dissociation constant (Kd), gene copy number, or specific EGFR genotypes (intron 1, -216G>T, -191C>A, 497Lys>Arg) were found between K-Ras-mutated and K-Ras-non-mutated tumors.
  • No correlation was observed between analyzed EGFR genotypes and EGFR expression.
  • EGFR expression was not related to gene copy number, and tumor EGFR gene copy number did not correlate with normal tissue copy number (mean tumor/normal ratio: 1.16).

Conclusions:

  • EGFR tumoral status is independent of K-Ras mutations in colorectal tumors.
  • These findings suggest that K-Ras mutation analysis does not impact the interpretation of EGFR status in colorectal cancer.

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