title: K-ras mutation status correlates with the expression of VEGFR1, VEGFR2, and PDGFRalpha in colorectal cancer.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, Mainz 55101, Germany. schimanski@1-med.klinik.uni-mainz.de
authors: Carl C
authors: CC
authors: Schimanski
authors: Tim
authors: T
authors: Zimmermann
authors: Irene
authors: I
authors: Schmidtmann
authors: Ines
authors: I
authors: Gockel
authors: Hauke
authors: H
authors: Lang
authors: Peter R
authors: PR
authors: Galle
authors: Markus
authors: M
authors: Moehler
authors: Martin R
authors: MR
authors: Berger
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D003062:Codon; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000032:analysis*; D015854:Up-Regulation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis*; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C501162:FLT1 protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins