In Situ Expression Of Hypoxia Inducible Factor 2-Alpha In Gliomas.

e13534Background: Hypoxia, a driver of malignancy, is fundamental to glioblastoma (GBM). Of the hypoxia inducible transcription factors (HIFs), HIF-2a is expressed in GBM tumor cells, responds to prolonged hypoxia, and is a prime candidate for HIF therapeutic targeting. PT2385 is a novel, orally available, first-in-class, HIF-2a inhibitor with a brain:plasma ratio of 0.9 in rats. To establish HIF-2a as a therapeutic target in GBM, in situ expression needs to be described. Methods: Twenty-two paraffin-embedded gliomas (grade II-IV) underwent immunohistochemistry for HIF-2a. After rehydration, a hot Tris EDTA pH 9.0 solution retrieved epitopes, non-specific sites were blocked, and HIF-2a antibody (Santa Cruz, sc-13596) was added. A horseradish peroxidase detection system identified staining. Representative samples were digitally scanned. Localization and quantification of HIF-2a was independently verified by a neuropathologist. Patient survival and molecular genetics were retrospectively collected with Inst...