PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN BRAIN-TUMORS - RELATION TO MALIGNANCY AND NECROSIS

TUMOR NECROSIS IS a common feature of malignant neoplasms. The pathoge nesis of tumor necrosis remains poorly documented. Recent evidence has shown a correlation between the presence of tumor necrosis and low co ntent of tissue plasminogen activator in brain tumors and significantl y 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. T he results were correlated with the presence of edema 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 tumo r necrosis (n = 6). The benign tumor samples (n = 96) had 3.5 times le ss PAI-1 than did the malignant tumors (n = 101). Tumor necrosis sampl es contained 3.8 times more PAI-1 than did the nonnecrotic malignant t umor samples (P < 0.000001). The benign meningioma samples showed a si milar ratio compared with their malignant counterparts (0.35 versus 1. 59 ng/mg, respectively, P = 0.0004). Regression analysis results showe d a strong correlation between PAI-1 and necrosis (r = 0.47, P < 0.000 0028) and, to a lesser extent, brain edema (r = 0.26, P = 0.001). A ne gative correlation between PAI-1 and tissue plasminogen activator leve ls almost reached statistical significance (P = 0.07). There was no co rrelation between PAI-1 content and the tumor size, duration of sympto ms, or the sex or age of the patients. The cellular localization and d istribution of PAI-I messenger ribonucleic acid were related primarily to vascular structures and necrotic foci. The expression of PAI-1 mes senger ribonucleic acid was also shown to be associated predominantly with necrotic areas in the tumor tissue. The results of this study ind icate that malignant transformation is associated with a significant i ncrease in PAI-1 and that PAI-1 may play an integral role in the patho genesis of tissue necrosis, perhaps via the inhibition of tissue plasm inogen activator and the promotion of microthrombosis.