Pi3K-mTOR Signaling and AMOG Expression in Epilepsy-associated Glioneuronal Tumors
Article first published online: 9 APR 2009
© 2009 The Authors. Journal Compilation © 2009 International Society of Neuropathology
Volume 20, Issue 1, pages 234–244, January 2010
How to Cite
Boer, K., Troost, D., Timmermans, W., Van Rijen, P. C., Spliet, W. G.M. and Aronica, E. (2010), Pi3K-mTOR Signaling and AMOG Expression in Epilepsy-associated Glioneuronal Tumors. Brain Pathology, 20: 234–244. doi: 10.1111/j.1750-3639.2009.00268.x
- Issue published online: 7 DEC 2009
- Article first published online: 9 APR 2009
- Received 9 November 2008; accepted 23 December 2008.
- adhesion molecule on glia;
- dysembryoplastic neuroepithelial tumor;
- malformations of cortical development;
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.