Expression of CD105 (Endoglin) in Hepatocellular Carcinoma and Correlation with Intrahepatic Metastasis: Analysis Using Tissue Microarrays and Comparison with Other Endothelial Marker

ABSTRACT

Neovascularization provides the route for nutrient supply to the tumor and the conduit for tumor cells to be shed into the circulation. CD31 is a pan-endothelial cell marker and CD105 is an active endothelial cell marker, but whether there is a link between CD105 expression and metastasis in Hepatocellular carcinoma (HCC) still remains unclear. A tissue microarray containing 38 HCCs and adjacent non-tumorous liver tissue samples was constructed. The microvessel density (MVD) of CD31, CD105, vWF and the expression of PCNA, VEGF were investigated in a HCC tissue microarray by immunohistochemistry. There was a significant difference between the score of MVD-CD31 in HCC (48.5 ± 29.7) and non-tumorous liver tissue (24.2 ± 22.3, P<0.01). The mean score of MVD-CD31 was higher in HCCs with high PCNA expression (68.4 ± 37.0) than in HCCs with low PCNA expression (37.9 ± 30.9, P = 0.012). MVD-CD105 and VEGF expression were significantly higher in HCC with intrahepatic metastasis (P < 0.01). Multivariate analysis confirmed that MVD- CD105 but not MVD-CD31 was an independent contributing factor to the intrahepatic metastasis. In conlusions, MVD-CD105 expression is associated with intrahepatic metastasis of HCC. Because CD105 is expressed in the activated endothelial cells of the newly formed blood vessels, neovascularization is important in the metastasis of HCC.