LGG-02. BIOCHEMICAL COMPOSITION AND BIOLOGICAL FUNCTION OF MYXOID MATRIX IN OPTIC GLIOMAS

PURPOSE: Optic gliomas are brain tumors characterized by slow growth, progressive loss of vision and limited therapeutic options. Optic gliomas contain various amount of myxoid matrix, which can represent majority of the tumor mass. We sought to investigate biological function and protein structure of the myxoid matrix in optic gliomas to identify novel therapeutic targets. EXPERIMENTAL DESIGN: We reviewed histological features of 120 optic gliomas, clinical imaging properties of 10 optic gliomas, analyzed vasculature by immunohistochemistry and electron microscopy of 12 optic gliomas and performed Liquid Chromatography–Mass Spectrometry on 10 snap-frozen age-, sex- and BRAF status- matched Nf1 wild-type optic gliomas, which varied in the amount of myxoid matrix. RESULTS: Optic gliomas contain varying amounts of myxoid matrix and are indistinguishable on imaging. Microvascular network of pilomyxoid astrocytoma, a subtype of optic glioma with abundant myxoid matrix, is characterized by the presence of endothelium-free channels in the myxoid matrix. Channels are connected to the main vascular network, show normal perfusion and lack thrombosis, likely due to extravasation of fibrin. The myxoid matrix is composed predominantly of the proteoglycan versican (VCAN) and its linking protein, a vertebrate Hyaluronan And Proteoglycan Link Protein 1 (HAPLN1). These proteins may limit effective delivery of chemotherapy to the tumor. CONCLUSIONS: Pediatric optic pathway gliomas maintain blood supply without endothelial cells by using invertebrate-like channels, which we termed “primitive myxoid vascularization.” Channels are formed within myxoid matrix, which lacks endothelium and absorbs fibrin. Targeting the optic glioma matrix enzymatically, similar to storage disorders, may decrease the tumor mass directly, as well as provide improved access of chemotherapy and molecularly targeted therapy to the tumor cells, providing increased treatment efficacy.