Expression and localization of vascular endothelial growth factor receptors in human hepatocellular carcinoma and non-HCC tissues

Flt-1 (VEGF receptor-1) and KDR/Flk-1 (VEGF receptor-2) are the high-affini ty receptors for the angiogenesis factor, vascular endothelial growth facto r (VEGF). VEGF expression has been confirmed in human hepatocellular carcin oma (HCC), and VEGF is thought to be involved in the angiogenesis within HC C tissues. However, expressions of VEGF receptors in HCC have not been repo rted. We immunohistochemically examined expressions and localizations of Fl t-1 and KDR in 28 surgically resected HCC tissues. In non-cancerous area, F lt-1 and KDR were mainly found in macrophages including Kupffer cells; both receptors were found in vascular endothelial cells in the portal veins and arteries within portal tracts; and KDR was also found in some sinusoidal e ndothelial cells. In cancerous area, Flt-1 and KDR were found in some macro phages, and also in the endothelial cells of intratumoral blood vessels. In 25 moderately and/or poorly differentiated HCCs, KDR expression in the blo od space endothelial cells was clear and continuous in 20 cases, and focal in 5 cases. These results suggest that there would be an angiogenesis mecha nism via VEGF/Flt-1 or VEGF/KDR in HCC, and the VEGF/KDR system would take a more important role.