Epithelial Expression of VEGF Receptors in Colorectal Carcinomas and their Relationship to Metastatic Status

Abstract

Background: Vascular endothelial growth factor (VEGF), originally identified as an endothelium-specific factor, can also bind to malignant cells, a mechanism by which a tumor could regulate its own progression. The biological effects of VEGF are mediated by three receptors (VEGFRs), VEGFR-1, VEGFR-2 and VEGFR-3. This study aimed at defining the expression of VEGFs in colorectal cancer (CRC) epithelia and their relationship to the metastatic status. Materials and Methods: Using immunohistochemistry, the levels of tumoral immunoreactivity for VEGFs in 105 non-metastatic, lymphogenously-metastatic and haematogenously-metastatic CRC specimens were assessed. Statistical analysis was performed using Fisher's exact probability test. Results: VEGFR-1 immunoreactivity was positive in only 50% of the cases. However lack of expression of VEGFR-1 was significantly associated with lymphogenous and haematogenous metastases. VEGFR-2 and VEGFR-3 were expressed in all investigated specimens to varying degrees. Low levels of VEGFR-2 were significantly associated with distant metastases. No significant changes were detected in VEGFR-3 expression. Conclusion: Epithelial expression of VEGFR-1 and VEGFR-2 appear to have a protective effect against tumor aggressiveness in CRC.