Plasminogen activator inhibitor-1 in brain tumors: relation to malignancy and necrosis.

Abstract

Tumor necrosis is a common feature of malignant neoplasms. The pathogenesis of tumor necrosis remains poorly documented. Recent evidence has shown a correlation between the presence of tumor necrosis and low content of tissue plasminogen activator in brain tumors and significantly higher levels of plasminogen activator inhibitor-1 (PAI-1) in human glioblastomas. We subjected fresh brain tumor tissue samples (n = 197) to an enzyme-linked immunosorbent assay to determine PAI-1 content. The results were correlated with the presence of edma and necrosis on imaging studies. The samples studied were from normal brain (n = 10), low-grade gliomas (n = 26), meningiomas (n = 47), acoustic neuromas (n = 18), glioblastomas (n = 45), metastases (n = 45), and areas of tumor necrosis (n = 6). The benign tumor samples (n = 96) had 3.5 times less PAI-1 than did the malignant tumors (n = 101). Tumor necrosis samples contained 3.8 times more PAI-1 than did the nonnecrotic malignant tumor samples (P < 0.000001). The benign meningioma samples showed a similar ratio compared with their malignant counterparts (0.35 versus 1.59 ng/mg, respectively, P = 0.0004). Regression analysis results showed a strong correlation between PAI-1 and necrosis (r = 0.47, P < 0.0000028) and, to a lesser extent, brain edema (r = 0.26, P = 0.001). A negative correlation between PAI-1 and tissue plasminogen activator levels almost reached statistical significance (P = 0.07). There was no correlation between PAI-1 content and the tumor size, duration of symptoms, or the sex or age of the patients. The results of this study indicate that malignant transformation is associated with a significant increase in PAlI1 and that PAI-1 may play an integral role in the pathogenesis of tissue necrosis, perhaps via the inhibition of tissue plasminogen activator and the promotion of microthrombosis.