Pi3K-mTOR signaling and AMOG expression in epilepsy-associated glioneuronal tumors.
Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs) represent the most frequent type of neoplasms in pediatric medically intractable epilepsy. Several data suggest a pathogenetic relationship between GGs and other glioneuronal malformations of cortical development (MCDs), including activation of the Pi3K-mTOR signaling pathway. To further reveal these pathogenetic similarities, we investigated immunocytochemically the expression of phosphorylated (p)-PDK1, p-AKT, p-mTOR, p-4E-BP1, p-eIF4G, p-p70S6K and p-S6, the effector proteins ERM (ezrin/radixin/moesin) and the pathway regulator AMOG (adhesion molecule on glia) in both GGs and DNTs. Components of the Pi3K-mTOR signaling pathway were observed in a higher percentage of neuronal cells in GGs compared with control cortex. In DNTs, the expression of these components was low and comparable with the expression in control samples. Strong immunoreactivity for ERM was observed in GGs, but not in DNTs. Additionally, AMOG was strongly expressed within GGs (but not in DNTs) in CD34-positive precursor cells. These findings support the previously suggested pathogenic relationship between GG and MCDs concerning activation of the Pi3K-mTOR signaling pathway and suggest a different pathogenetic origin for DNTs. The strong expression of AMOG within the precursor cells of GG may represent an additional marker for the diagnostic evaluation of these glioneuronal lesions.
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
Karin
K
Boer
Dirk
D
Troost
Wendy
W
Timmermans
Peter C
PC
van Rijen
Wim G M
WG
Spliet
Eleonora
E
Aronica
D000251:Adenosine Triphosphatases / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001344:Autopsy; D001932:Brain Neoplasms / Q000150:complications / Q000473:pathology*; D027682:Cation Transport Proteins / Q000096:biosynthesis*; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis*; D002540:Cerebral Cortex / Q000473:pathology; D002648:Child; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004351:Drug Resistance; D004827:Epilepsy / Q000150:complications / Q000473:pathology*; D005260:Female; D018303:Ganglioglioma / Q000150:complications / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D018242:Neuroectodermal Tumors, Primitive / Q000150:complications / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D038601:Ribosomal Protein S6 / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000473:pathology; D000099149:Ezrin
D000251:Adenosine Triphosphatases; D018952:Antigens, CD34; D027682:Cation Transport Proteins; D015816:Cell Adhesion Molecules, Neuronal; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D038601:Ribosomal Protein S6; D058570:TOR Serine-Threonine Kinases; D000099149:Ezrin; C504190:ATP1B2 protein, human; C071058:moesin; C071776:radixin; C546842:MTOR protein, human