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

Abstract

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. 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. 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). 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.