gms | German Medical Science

56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

Molecular neuropathology of epilepsy-associated focal cortical dysplasias: alterations of PI3K pathway components in focal cortical dysplasias with Taylor type balloon cells

Molekulare Neuropathologie Epilepsie-assoziierter Fokaler Cortikaler Dysplasien: Veränderungen der PI3K-Signaltransduktion in Fokalen Cortikalen Dysplasien vom Taylor Ballonzellen-Typ

Meeting Abstract

  • corresponding author M. Majores - Institut für Neuropathologie, Universitätsklinikum Bonn
  • V. Schick - Institut für Neuropathologie, Universitätsklinikum Bonn
  • S. Normann - Institut für Neuropathologie, Universitätsklinikum Bonn
  • A. Koch - Institut für Neuropathologie, Universitätsklinikum Bonn
  • C. E. Elger - Klinik für Epileptologie, Universitätsklinikum Bonn
  • J. Schramm - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Bonn
  • A. J. Becker - Institut für Neuropathologie, Universitätsklinikum Bonn

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. DocP010

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2005/05dgnc0278.shtml

Published: May 4, 2005

© 2005 Majores et al.
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Outline

Text

Objective

Focal cortical dysplasia with Taylor type balloon cells (FCDIIb) constitutes a frequent and histopathologically distinct finding in patients with pharmacoresistant focal epilepsies. Recent data indicate a pathogenetic role of TSC1, known to be mutated in Tuberous Sclerosis (TSC), for FCDIIb. TSC1 represents a key factor in the phosphatidylinositol 3-kinase (PI3K) pathway. In order to further elucidate the molecular pathology of FCDIIb, we have analyzed two additional major components of the PI3K-cascade in FCDIIb, i.e. PTEN and Akt which operate upstream from TSC1.

Methods

Mutational screening of PTEN was performed by single-strand conformation polymorphism analysis (SSCP) in 37 FCDIIb compared to 100 controls. Immunohistochemistry with antibodies against phospho-Akt (Ser473) was carried out in FCDIIb (n=37).

Results

We found several silent polymorphisms of PTEN in exon 2 (n=2) and exon 8 (n=1) as well as an amino-acid exchange at position 279 (exon 8) with replacement of phenylalanine by leucine (F279L) in one patient. Using laser assisted microdissected cell samples, this alteration was only found in FCDIIb components but not in adjacent CNS tissue. We found an increased immunoreactivity for phospho-Akt in balloon cells and dysplastic neurons but not in adjacent normal CNS tissue.

Conclusions

These data demonstrate alterations of the PI3K pathway components PTEN and Akt in FCDIIb. This is in line with the hypothetical role of the PI3K cascade in focal cortical dysplasias with Taylor type balloon cells.

Supported by DFG (SFB TR3) and BONFOR