Expression And Its Clinical Significance Of VEGF-C And VEGF-D In Hypopharyngeal Cancer

Background: Vascular endothelial growth factor(VEGF) also named vascular permeability factor(VPF),is an important positive regulator for angiogenesis. This is one target of the anticancer research. Discovered members of VEGF family include: VEGF-A,VEGF-B,VEGF-C,VEGF-D,VEGF-E and placenta growth factor(PLGF). Receptors of VEGF are VEGFR-1(flt-1),VEGFR-2(flk-1/KDR),VEGFR-3(flt-4) and neuropilin (NPR1/NPR2).Members of this family can selectively promote mitosis of vascular endothelial cells or lymphatic endothelial cells, stimulate endothelial cells to proliferate and induce angiogenesis. They also enhance the permeability of microvessels, help to establish capillary vessels net. The presence of metastases in lymph nodes is a strong indicactor of poor prognosis for patient with hypopharyngeal cancer. A number of clinical and experimental studies suggests that the expression of vascular endothelial growth factor (VEGF)-C and/or VEGF-D could stimulate lymphangiogenesis in tumors by activating their receptors on the lymphatic endothelial cells, then enhance the incidence of lymph node metastasis. In addition ,inhibition of VEGFR-3 signaling could suppress tumor lymphangiogenesis and metastasis to lymph nodes, thus, inhibition of lymphangiogenesis can be expected to be a new method of blocking tumor metastasis. In this study, we aimed toclarity the relation between expression of VEGF-C and VEGF-D and lymphatic metastasis in hypopharyngeal carcinoma.Methods: 64 cases with hypopharyngeal carcinoma were collected from Qilu hospital, all specimen were embedded in paraffine and sectioned routinely. Thesections were stained with the immunohistochemistry technique, and observed under the light microscope.Results: According to the expression degree of VEGF-C and VEGF-D with immunohistochemistry, 64 cases specimens were classified into three groups: the negative group, focal expression group and diffuse expression group. The expression rate was 65.6% for VEGF-C protein and 57.8% for VEGF-D protein. The difference was not statistically significant(P > 0.05). In VEGF-C negative group, focal expression group and diffuse expression group, the rates of cases with lymph node metastasis were 18.2%, 73.1%, 93.8%, there was statistically significance(P < 0.01). In VEGF-D negative group, focal expression group and diffuse expression group, the rates of cases with lymph node metastasis were25.9%, 78.3%, 92.9%, there was statistically significance(P<0.01).The results suggest that there is a significant correlation between the expression of VEGF-C and VEGF-D and lymph node metastasis, but the expression of VEGF-C and VEGF-D is not related with venous invasion.Conclusions: The expression of VEGF-C and VEGF-D in hypopharyngeal carcinoma may predict lymph node metastasis, which may suggest the poor prognosis of the patients with hypopharyngeal carcinoma. Restraining of the expression of VEGF-C and VEGF-D may be a promising target for new therapentic strategies in hypopharyngeal carcinoma.