CIRCULATING VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) IS A POSSIBLE TUMOR-MARKER FOR METASTASIS IN HUMAN HEPATOCELLULAR-CARCINOMA

Vascular endothelial growth factor (VEGF) is closely related to angiog enesis in Various human cancers. However,little is known of its circul ating levels in hepatocellular carcinoma (HCC). We examined circulatin g VEGF levels in chronic liver disease to assess their clinical signif icance. Plasma VEGF concentrations were determined, by enzyme immunoas say, in patients with chronic hepatitis (CH;n =36), liver cirrhosis (L C; n = 77), and HCC (n = 86) for a cross-sectional study. Plasma VEGF levels in healthy controls (n = 20) and CH, LC, and HCC patients were 17.7 +/- 5.4 (mean +/- SD), 30.6 +/- 22.8, 34.4 +/- 27.0, and 51.1 +/- 71.9 pg/ml, respectively. The levels were significantly elevated in t he HCC group, compared with the control, CH, and LC groups. Plasma VEG F levels in stage I, II, III, IVA, and IVB HCC patients were 27.6 +/- 16.1, 26.5 +/- 13.7, 35.8 +/- 15.3, 45.4 +/- 39.4, and 103.1 +/- 123.2 pg/ml, respectively. The stage IVB patients with remote metastasis sh owed significantly marked elevation compared with the patients at the other stages. Platelet numbers were weakly correlated with plasma VEGF levels in the HCC group. Plasma VEGF level was highly elevated in pat ients with HCC, particularly those with metastatic disease. We conside r that plasma VEGF is a possible tumor marker for metastasis of HCC. C irculating VEGF may be derived mainly from the large burden of tumor c ells, and partly from platelets activated by the vascular invasion of HCC cells.