PROGNOSTIC-SIGNIFICANCE OF PROTEOLYTIC-ENZYMES IN HUMAN BRAIN-TUMORS

Proteases and their inhibitors have been shown to play roles in tumor invasion and metastasis in a number of experimental models. Recently, relative increases in the amounts of urokinase type plasminogen activa tor (uPA) and plasminogen activator inhibitor-1 (PAI-1) in tumor sampl es have been correlated with poorer pathological grade, shorter diseas e-free interval, and shorter survival. To date, all studies investigat ing the prognostic significance of proteases and their inhibitors have been limited to extracranial cancer. In this article, we review the l iterature and present our data on the prognostic significance of prote ases in human brain tumors. High levels of uPA were seen in malignant glioma and metastatic tumors (n = 82), whereas normal levels of uPA we re found in tow-grade gliomas. Analysis with magnetic resonance imagin g (MRI) demonstrated a significant correlation between high levels of uPA and necrosis and edema (n = 50; P < 0.05). Similarly, patients wit h high levels of uPA had shorter survival than did patients with low l evels of uPA. Tissue-type plasminogen activator (tPA), which was virtu ally absent in glioblastoma multiforme (GBM), colon, lung, and breast metastasis, was found in normal quantities in anaplastic astrocytoma ( AA), low-grade glioma (LGG), and meningioma. Melanoma had significantl y more tPA activity than normal brain did. A reverse correlation was f ound between tPA and MRI findings of necrosis, enhancement, and edema. Similarly, patients with no detectable tPA activity had shorter survi val than did patients with detectable tPA activity. We conclude that h igh levels of uPA and absent tPA activity correlate with histologicall y malignant brain tumors, aggressive characteristics, and shorter surv ival.