PLASMINOGEN ACTIVATORS AND PLASMINOGEN-ACTIVATOR INHIBITORS IN BLOOD AND TUMOR FLUIDS OF PATIENTS WITH OVARIAN-CANCER

We quantitated urokinase and tissue plasminogen activator (u-PA, t-PA) , plasminogen activator inhibitor 1 and 2 (PAI-1, PAI-2), and fibrinol ytic activity in peripheral blood (PB), tumour blood (TB), peritoneal/ ascitic fluid (PAF) and cystic fluid (CF) from 104 patients with benig n and 36 patients with malignant ovarian tumours, and in peripheral bl ood from 62 healthy controls. PB levels of u-PA were higher in patient s with benign and malignant tumours than in controls. High concentrati ons of u-PA were found in CF, but not in TB, suggesting that u-PA is r eleased by the tumour tissue, but not by the tumour vasculature. PB le vels of t-PA were higher in both tumour groups than in controls. Incre ased levels of t-PA were found in TB, but not in CF, indicating that t -PA is released by the tumour vasculature, but not by the tumour tissu e. PB levels of PAI-1 were higher in patients with both benign and mal ignant tumours than in controls. High levels of PAI-1 were present in both TB and CF from malignant tumours, suggesting that PAI-1 is releas ed from the tumour vasculature as well as the tumour tissue. Elevated concentrations of PAI-I were found in CF, but not in TB, indicating re lease from the tumour tissue, but not from the vasculature. High level s of t-PA, PAI-1 and PAI-2 were found in PAF of malignant tumours, and resorption from this compartment may explain elevated PB levels in pa tients with ascites. None of the PAs/PAIs proved useful as a PB marker for detection of early stage ovarian cancer. However, an index based on PAF levels of t-PA and PAI-1 discriminated between malignant and be nign ovarian cysts in the absence of ascites. In addition, our study s tresses the importance of including patients with benign tumours as we ll as healthy controls when markers for malignant tumours are evaluate d.