UROKINASE AND PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 IN PULMONARY ADENOCARCINOMA

The urokinase pathway of plasminogen activation is involved in proteol ytic degradation of various tissues, including dissolution of the extr acellular matrix and basement membranes during the process of cancer c ell invasion. We have studied the prognostic value of urokinase-type p lasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAI-1) in tumor extracts from 106 patients with adenocarcinoma of the lung. uPA and PAI-1 levels were determined by sandwich enzyme-linked immunosorbent assays. No correlation was found between uPA and PAI-1 ( r = 0.23). High PAI-1 levels were significantly associated with short- duration overall survival (P = 0.017), while uPA levels showed no sign ificant association with overall survival. Relating the levels of PAI- 1 to other prognostic factors such as stage and age, no significant co rrelations were found. The prognostic impact of uPA and PAI-1 were inv estigated together with other prognostic factors in Cox multivariate a nalysis. PAI-1 was found to be an independent prognostic variable for survival, the relative risks being 1.5 (low versus medium PAI-1 values (95% confidence interval, 1.2-1.8) and 2.2 (low versus high (95% conf idence interval, 1.8-2.6)). In patients with stage I disease (69 patie nts) high levels of PAI-1 were significantly associated with poor prog nosis compared to low levels (P = 0.037). These data indicate that PAI -1 is a potentially important prognostic factor in pulmonary adenocarc inoma and may as such be used to select patients with low stage and po or prognosis for adjuvant therapy subsequent to complete surgical rese ction.