title: Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.
abstract: Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Buccoliero
authors.forename: Chiara
authors.initials: C
authors.lastname: Caporalini
authors.forename: Flavio
authors.initials: F
authors.lastname: Giordano
authors.forename: Federico
authors.initials: F
authors.lastname: Mussa
authors.forename: Mirko
authors.initials: M
authors.lastname: Scagnet
authors.forename: Selene
authors.initials: S
authors.lastname: Moscardi
authors.forename: Gianna
authors.initials: G
authors.lastname: Baroni
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Genitori
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Taddei
mesh_terms: D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014402:Tuberous Sclerosis / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D005974:Glutamate-Ammonia Ligase