Epithelioid glioblastoma with microglia features: potential for novel therapy.

Brain Pathology
Nami NakagomiSeiichi Hirota

Abstract

Epithelioid glioblastoma (E-GBM) was recently designated as a subtype of glioblastoma (GBM) by the World Health Organization (2016). E-GBM is an aggressive and rare variant of GBM that primarily occurs in children and young adults. Although most characterized cases of E-GBM harbor a mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600 (BRAF-V600E), in addition to telomerase reverse transcriptase promoter mutations and homozygous CDKN2A/B deletions, the origins and cellular nature of E-GBM remain uncertain. Here, we present a case of E-GBM that exhibits antigenic and functional traits suggestive of microglia. Although no epithelial [e.g., CKAE1/3, epithelial membrane antigen (EMA)] or glial (e.g., GFAP, Olig2) markers were detected by immunohistochemical staining, the microglial markers CD68 and Iba1 were readily apparent. Furthermore, isolated E-GBM-derived tumor cells expressed microglial/macrophage-related genes including cytokines, chemokines, MHC class II antigens, lysozyme and the critical functional receptor, CSF-1R. Isolated E-GBM-derived tumor cells were also capable of phagocytosis and cytokine production. Treating E-GBM-derived tumor cells with the BRAF-V600E inhibitor, P...Continue Reading

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