EXPRESSION AND CELLULAR-LOCALIZATION OF MESSENGER-RNA FOR PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 IN HUMAN ASTROCYTOMAS IN-VIVO

We investigated the expression and cellular localization of plasminoge n activator inhibitor type 1 (PAI-1) in human astrocytoma in vivo. Nor thern blot and densitometric quantitation of PAI-1 mRNA indicated that PAI-1 transcripts were significantly higher in human malignant astroc ytomas and especially in glioblastomas then in low-grade gliomas and n ormal brain tissues in vivo. Using in situ hybridization with paraffin -embedded surgical specimens of human gliomas and normal brain tissues , PAI-1 mRNA was abundantly expressed in glioblastomas. PAI-1. mRNA wa s localized mainly in tumor cells and endothelial cells. The distribut ion of PAI-1 mRNA expression was particularly abundant around areas of vascular proliferation and in remnant tumor cells surrounding necroti c foci. PAI-1 mRNA was also expressed in both the tumor and endothelia l cells of anaplastic astrocytomas, whereas it was not expressed or on ly weakly expressed in low-grade astrocytomas or normal brain tissues. These results suggest that high expression of PAI-1 is associated wit h the malignant progression of astrocytic tumors and that excessive PA I-1 expression might be associated with intratumoral necrosis in gliob lastomas.