CD44 and VEGF expression in extrahepatic metastasis of human hepatocellular carcinoma

We investigated the correlation between vascular endothelial growth factor (VEGF) and CD44 expression in hepatocellular carcinoma (HCC) and the frequency of extrahepatic metastasis, in order to evaluate the influence of vascular growth and adhesion molecules in facilitation of distant metastasis.We obtained materials from primary lesions of HCC with no extrahepatic metastasis (control group) and primary lesions and metastatic lesions with extrahepatic metastasis (metastasis group). Immunohistochemical staining was performed using anti-human CD44v3 monoclonal antibodies and anti-human VEGF ab-3 monoclonal antibodies. Although pathological parameters such as tumor size, differentiation, capsule formation, and vascular invasion were analyzed, there was no marked difference among the groups.Percentages of nodules with VEGF-positive tumor and sinusoidal cells were low in primary lesions of the control and metastasis groups, while high in metastatic lesions in the metastasis group. On the other hand, percentages of nodules with CD44-positive tumor and sinusoidal cells were low in primary lesions of the control group, while high in primary lesions and metastatic lesions of the metastasis group.The present study demonstrated that CD44 expression in primary lesions is related to a higher frequency of extrahepatic metastasis, suggesting that this is a clinicopathologically useful parameter in predicting the occurrence of distant metastasis.