OUP user menu

Microvessel Density, Vascular Endothelial Growth Factor and Its Receptors Flt-1 and Flk-1/KDR in Hepatocellular Carcinoma

Irene O.L. Ng MD, Ronnie T.P. Poon MS, Joyce M.F. Lee MSc, Sheung T. Fan MD, Matthew Ng MD, Wai K. Tso MD
DOI: http://dx.doi.org/10.1309/FXNL-QTN1-94FH-AB3A 838-845 First published online: 1 December 2001

Abstract

Assessment of angiogenesis may yield important information for an effective antiangiogenic treatment for hepatocellular carcinoma (HCC) because HCC is characteristically hypervascular. We examined the relationship of microvessel density (MVD), vascular endothelial growth factor (VEGF), and VEGF receptors Flt-1 and Flk-1/KDR in 50 patients with HCC and in 3 hepatoma cell lines. VEGF messenger RNA (mRNA) was overexpressed in 26 tumors (52%), and the 3 VEGF isoforms (121, 165, and 189) were present in high frequencies. Flt-1 mRNA was overexpressed in 34 tumors (68%), with levels significantly increased in HCCs compared with the nontumorous livers. Tumor Flt-1 mRNA significantly correlated with tumor VEGF mRNA levels. Within the group of tumors 8.5 cm or less in diameter, tumors with intrahepatic metastasis in the form of tumor microsatellite formation had significantly higher VEGF mRNA levels. MVD assessed by immunohistochemical analysis with CD34 antibody was inversely related to tumor size. Angiogenesis as assessed by MVD and tumor VEGF expression seems to have a more important role in tumor growth and intrahepatic metastasis in smaller HCCs. The differential up-regulation of Flt-1 suggests that it may have an important role in angiogenesis in HCC.

Key Words:
  • Microvessel density
  • Vascular endothelial growth factor
  • VEGF
  • Flt-1
  • Flk-1/KDR
  • Hepatocellular carcinoma