Plasminogen activators and inhibitors in gliomas: an immunohistochemical study

The tissue (tPA) and urokinase (uPA) types of plasminogen activator and the plasminogen activator inhibitor 1 (PAI-1) are enzymatic proteins that may play an important role in the degradation of the extracellular matrix in physiologic and neoplastic conditions. In particular, urokinase may underlie key properties of malignant cells, such as invasiveness and dissemination. We have studied the immunohistochemical distribution of tPA, uPA, and PAI-1 in 24 human gliomas, including seven well-differentiated astrocytomas, three oligodendrogliomas, six anaplastic astrocytomas, and eight glioblastomas multiforme. All anaplastic astrocytomas and glioblastomas showed numerous neoplastic cells immunoreactive for uPA, but not for tPA. In contrast, low-grade gliomas were negative for uPA, but contained some tPA-immunoreactive cells. Endothelial cells of vessels in non-neoplastic and neoplastic brain were immunoreactive 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 gliomas suggest that this fibrinolytic protein plays a significant role in the invasive properties of these neoplasms.