PLASMINOGEN ACTIVATORS AND INHIBITORS IN GLIOMAS - AN IMMUNOHISTOCHEMICAL STUDY

The tissue (tPA) and urokinase (uPA) types of plasminogen activator an d the plasminogen activator inhibitor 1 (PAI-1) are enzymatic proteins that may play an important role in the degradation of the extracellul ar matrix in physiologic and neoplastic conditions. In particular, uro kinase may underlie key properties of malignant cells, such as invasiv eness and dissemination. We have studied the immunohistochemical distr ibution of tPA, uPA, and PAI-1 in 24 human gliomas, including seven we ll-differentiated astrocytomas, three oligodendrogliomas, six anaplast ic astrocytomas, and eight glioblastomas multiforme. All anaplastic as trocytomas and glioblastomas showed numerous neoplastic cells immunore active for uPA, but not for tPA. In contrast, low-grade gliomas were n egative for uPA, but contained some tPA-immunoreactive cells. Endothel ial cells of vessels in non-neoplastic and neoplastic brain were immun oreactive for tPA, but not for uPA or PAI-1. Non-neoplastic glia were unreactive for tPA, uPA, and PAI-1. Small anaplastic cells present in three glioblastomas showed immunoreactivity for PAI-1. The presence of a large number of uPA-immunoreactive neoplastic cells in high-grade g liomas suggest that this fibrinolytic protein plays a significant role in the invasive properties of these neoplasms.