The Expression Of VEGF-C And VEGF-D And Their Receptor VEGFR-3 In Colorectal Cancer And Its Influence To Metastasis And Prognosis

Vascular endothelial growth factor-C(VEGF-C)and VEGF-D are two new members of the vascular endothelial growth factor(VEGF)family of cytokines. It is reported that VEGF-C and -D have lymphangiogenic actions in cancers and can promote lymph node metastasis. Lymphangiogenesis, the development of new lymph vessels, is a relatively new area of clinical investigation. Increased interest in this field has been heightened by the discovery of the two new VEGF family members, which possess lymphangiogenic roles. The role of VEGF-C and VEGF-D in colorectal cancers(CRCs) remains unclear, with conflicting reports in the published literature. In our study, the protein expression of VEGF-C, VEGF-D, VEGFR-3, podoplanin, CD34 and Ki-67 in CRCs were detected by immunohistochemistry and double-labelling immunohistochemistry. MLD and MVD were evaluated by immunohistochemistry with anti-human podoplanin and CD34 antibody respectively. The mRNA expression of VEGF-C and its receptor VEGFR-3 in CRCs were detected by RT-PCR. Moreover, the relationship between expression of VEGF-C, VEGF-D and its receptor VEGFR-3 with MLD, MVD, clinicopathological features and prognosis of patients with CRC was retrospectively analyzed. The main results and conclusions are as follows:VEGF-C, VEGF-D and VEGFR-3 protein or VEGF-C and VEGFR-3mRNA level of tumor tissues was significantly higher than that in normal mucosa. Moreover, the expression of VEGF-C or VEGF-D was significantly coincident and correlated with that of VEGFR-3. It suggests that the VEGF-C/-D-VEGFR-3 signal pathway might be of great importance in colorectal carcinogenesis.VEGF-C and VEGF-D protein or VEGF-C mRNA expression was significantly correlated with MLD in CRCs,especially at the invasive edge. Futhermore, Ki-67 expression of lymphatic endothelium was significantly increase in CRCs with VEGF-C or VEGF-D highly expression. According to these results, we presume that VEGF-C and VEGF-D play an important role in peritumoral lymphangiogenesis.The VEGF-C and VEGF-D protein, VEGF-C mRNA expression or MLD was significantly correlated with lymphatic involvement and lymph nodes metastasis in CRCs. This means that VEGF-C and VEGF-D can promote lymph node metastasis by inducing lymphangiogenesis especially at the edge of CRC, and VEGF-C, VEGF-D or MLD may serve as useful markers to predict lymph node metastasis.The 5-year survival rate was significantly reduced in patients with positive VEGF-C/-D or higher MLD or MVD, which suggests that they were significantly correlated with prognosis and might be useful markers to evaluate prognosis of patient with CRC.