gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

Mutational and immunohistochemical analysis of ezrin-, radixin-, moesin (ERM) proteins in epilepsy associated glioneuronal lesions

Genotypische und immunhistochemische Analyse der Ezrin-, Radixin- und Moesin- (ERM) Proteine bei Epilepsie-assoziierten glioneuronalen Läsionen

Meeting Abstract

  • corresponding author M. Majores - Institut für Neuropathologie, Universtitätsklinikum Bonn
  • V. Schick - Institut für Neuropathologie, Universtitätsklinikum Bonn
  • G. Engels - Institut für Neuropathologie, Universtitätsklinikum Bonn
  • J. Fassunke - Institut für Neuropathologie, Universtitätsklinikum Bonn
  • C.E. Elger - Klinik für Epileptologie, Universtitätsklinikum Bonn
  • J. Schramm - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Bonn
  • I. Blumcke - Institut für Neuropathologie, Universitätsklinikum Erlangen
  • A.J. Becker - Institut für Neuropathologie, Universtitätsklinikum Bonn

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocP 05.73

The electronic version of this article is the complete one and can be found online at:

Published: May 8, 2006

© 2006 Majores et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Glio-neuronal lesions are frequently observed in biopsy specimens obtained from patients with pharmacoresistant epilepsies, comprising focal cortical dysplasias (FCD) and gangliogliomas. Recent findings characterize the phosphoinositide 3-kinase (PI3K) pathway and tuberin/hamartin signaling cascade to be compromized in these lesions. Ezrin, radixin and moesin (ERM-/band-4.1 proteins) genes represent downstream effectors of the PI3K-pathway, are involved in cytoskeleton-membrane interference, cell growth, migration and differentiation and harbor tumor suppressor motifs. Accumulation of band-4.1 proteins has been identified in cortical tubers of tuberous sclerosis patients, which share neuropathological similarities with FCD and gangliogliomas.

Methods: We have studied the immunohistochemical distribution pattern of ERMs in gangliogliomas (n=20) and focal cortical dysplasias (FCDIIa, n=8; FCDIIb, n=37). Mutational screening of the ezrin and radixin genes was performed by PCR-SSCP and sequencing analyses.

Results: Aberrant accumulation of ERMs was observed in dysplastic neurons of FCDs and gangliogliomas as well as in balloon cells. Adjacent brain tissue without structural abnormalities was used as control and showed only faint neuropil staining. Mutational screening revealed silent polymorphisms in the ezrin gene in two individuals suffering from FCDIIb. A transition from G to A of radixin exon 2 resulted in an exchange of valine by isoleucine at codon 50 in an additional FCDIIb specimen. These sequence alterations were not found in controls.

Conclusions: The present data suggest accumulation of ERM expression in dysplastic cellular components but do not favor mutational events of ERM in the pathogenesis of FCDs or gangliogliomas. Aberrant expression of ERMs is, however, compatible with a compromised PI3K-pathway in glio-neuronal lesions characterized by abnormal cellular differentiation and aberrant network formation.

Funding supported by: Our work is supported by DFG (SFB TR3), BONFOR, Deutsche Krebshilfe and BMBF. We especially thank Professor Shoichiro Tsukita and colleagues for kindly providing antibodies against the ERM proteins.