K-ras mutation status correlates with the expression of VEGFR1, VEGFR2, and PDGFRalpha in colorectal cancer

Int J Colorectal Dis. 2010 Feb;25(2):181-6. doi: 10.1007/s00384-009-0843-7. Epub 2009 Nov 20.

Abstract

Aim: We initiated this study in order to analyze whether the expression level of targeted receptor tyrosine kinases (RTK) is associated with the K-ras mutation status.

Methods: The expression pattern of VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta, and EGFR1 was analyzed in 93 samples of human colorectal carcinoma samples and correlated with the K-ras mutation status as identified by PCR-RFLP.

Results: VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta, and EGFR1 were expressed at relevant levels in 95%, 46%, 46%, 85%, 62%, and 82%, respectively. K-ras mutations were present in 53% (codon 12, 47%; codon 13, 6%). Expression of VEGFR1 (P = 0.0263), VEGFR2 (P = 0.0466), and PDGFRalpha (P = 0.0063) was significantly linked to K-ras codon 12 or 13 mutation. In addition, co-expression of VEGFR2 and PDGFRalpha was significantly associated with K-ras mutation (P = 0.0145).

Conclusion: Our data reveal that specific RTKs are over-expressed in K-ras mutated cancers. It needs to be addressed in prospective studies whether these patients will benefit from tyrosine kinase inhibitors more than K-ras wild-type.

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Codon
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Mutation*
  • Neoplasm Staging
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Receptor, Platelet-Derived Growth Factor alpha / analysis*
  • Up-Regulation
  • Vascular Endothelial Growth Factor Receptor-1 / analysis*
  • Vascular Endothelial Growth Factor Receptor-2 / analysis*
  • ras Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • Codon
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • FLT1 protein, human
  • Receptor, Platelet-Derived Growth Factor alpha
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins