Investigation On Relation Between The Espression Of VEGF-C,VEGFR-3 And Podoplanin And Lymphatic Metastasis In Human Hepatocellular Carcinoma

Objective Hepatocellular carcinoma(HCC) is one of the most common malignancies worldwide and the third leading cause of death in China. Lymphatic spread is an important clinical determinant for the prognosis of hepatocellular carcinoma (HCC), but little is known about the control of lymphangiogenesis in HCC. Vascular endothelial growth factor-C have been shown to promote tumour lymphangiogenesis, the metastatic spread of tumour cells to lymph nodes and, in some cases, distant organ metastasis in multiple animal models of cancer. Podoplanin, a 38-kd typeâ… membrane glycoprotein, is specifically expressed in the endothelium of lymphatic capillaries. To observe the expressions of vascular endothelial growth factor C(VEGF-C),vascular endothelial growth factor receptor 3(VEGFR-3) in Hepatocellular carcinoma and explore their relationship in carcinoma.To provide the morphology data for the study on the molecular mechanism of tumor metastasis, we observed the expression of podoplanin on the lymphatics in HCC.Methods We observed the expression of podoplanin, VEGF-C and VEGFR-3 by Non-Biotin immunohistochemistry. Lymphatic micro-vessel density (LMVD) in hepatocellular carcinoma was calculated by using podoplanin as the specific marker of lymphatic endothelium.Results VEGF-C and VEGFR-3 positive products were detected in tumor cell plasm, the expression positive rates of VEGF-C and VEGFR-3 in hepatocellular carcinoma were obviously higher than those in normal hepatic tissues(P<0.01) . Podoplanin has not been stained on blood vessels, but podoplanin was positively expressed on the human HCC lymphatics. The expression positive rate of LMVD in HCC tissues and adjacent non-tumorous liver was obviously higher than that in normal hepatic tissues (P<0.01).Conclusions Overexpressions of VEGF-C in Hepatocellular carcinoma can promote lymphangiogenesis in tumor by combining its receptor VEGFR-3.Podoplanin choosed to express in lymphatics in the HCC and could correctly distinguish the blood vessels and lymphatic vessels, could be regarded as the specific marker to mark lymphatic vessel. The positive rate of podoplanin expression were increased in HCC and the group with lymph nodes metastasis, and therefore, Our study suggests that the count of Lymphatic vessels increased likely contributes to lymphatic spread of HCC.