EXPRESSION OF VASCULAR-PERMEABILITY FACTOR VASCULAR ENDOTHELIAL GROWTH-FACTOR IN HUMAN HEPATOCELLULAR-CARCINOMA/

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is unique in its ability to promote vascular permeability and e ndothelial cell growth, and its role in tumor development has received considerable attention. In this report, we describe the elevation of VPF/VEGF transcript expression in human hepatocellular carcinoma. Surg ical samples of 23 patients with hepatocellular carcinoma were studied using reverse transcription-PCR analysis. The oligonucleotide primers were designed to amplify all four known splicing variants that could be expressed in the samples studied. Sixteen cases showed VPF/VEGF tra nscript expression in the tumor (16/23, 69.6%), whereas only 9 of the 23 patients showed it in the corresponding nontumoral part. There was no difference between the pattern of expression of VPF/VEGF isoforms i n tumoral and nontumoral tissues. VPF/VEGF mRNA expression in the live r tumors was associated with fibrous capsule formation and septal form ation (P < 0.05 respectively, Fisher's exact P test). In situ hybridiz ation confirmed the presence of VPF/VEGF mRNA expression in tumor cell s and less intensely in hepatocytes of nontumoral liver. We also found that VPF/VEGF expression In the tumor cell was increased in the area adjacent to necrotic regions (presumably hypoxic regions). As a regula tor of vascular permeability and endothelial cell growth factor, VPF/V EGF may play an important role in the development of hepatocellular ca rcinoma.