Clinical significance of urokinase-type plasminogen activator activity in hepatocellular carcinoma

Background and Methods: The plasminogen activation system plays a crucial r ole in the process of cancer invasion and metastasis. To evaluate the most effective factor in the invasion, metastasis and prognosis of hepatocellula r carcinoma (HCC), we examined urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor (PAI)-1, PAI-2 and uPA activity by enzyme-l inked immunosorbent assays (ELISA) in HCC tissues obtained from 46 patients . The results were compared with the patients' clinicopathological features and prognoses. Results: Of the clinicopathological features, only histological portal invo lvement or intrahepatic metastasis, or both (INV), was significantly correl ated to the disease-free survival rates (DFS; P < 0.05). The levels of uPA, PAI-1 and PAI-2 antigens were significantly associated with INV and histol ogical grade. The DFS was not different, however, between cases with uPA, P AI-1 and PAI-2 values above and below the median. The high levels of uPA ac tivity were closely related to INV (P < 0.001), and the activity gradually raised histological grades (P < 0.0001). The DFS was significantly differen t between patients with uPA activity below and above the median (0.70 ng/mL ; P = 0.0092); it was also significantly different between such patients wi thout INV (P < 0.05). Conclusions: Urokinase-type plasminogen activator activity may be the most sensitive factor affecting HCC invasion in the plasminogen activation syste m and a strong predictor for the recurrence of HCC. We suggest that cases w ith uPA activity of more than 0.70 ng/mL should be carefully followed up fo r possible HCC recurrence. (C) 2000 Blackwell Science Asia Pty Ltd.