K-ras mutation status correlates with the expression of VEGFR1, VEGFR2, and PDGFRalpha in colorectal cancer.
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.
Schimanski
Carl C
CC
First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, Mainz 55101, Germany. schimanski@1-med.klinik.uni-mainz.de
Zimmermann
Tim
T
Schmidtmann
Irene
I
Gockel
Ines
I
Lang
Hauke
H
Galle
Peter R
PR
Moehler
Markus
M
Berger
Martin R
MR
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*
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