Artikel
IDH1 R132H and BRAF V600E mutations in long-term epilepsy-associated tumors
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Autoren
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Alexander Grote
- Department of Neurosurgery, University of Bonn, University Medical Center, Bonn
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Albert J. Becker
- Institute for Neuropathology, University of Bonn, University Medical Center, Bonn
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Johannes Schramm
- Department of Neurosurgery, University of Bonn, University Medical Center, Bonn
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Andreas von Deimling
- Department of Neuropathology, University Heidelberg, Heidelberg
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Matthias Simon
- Department of Neurosurgery, University of Bonn, University Medical Center, Bonn
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David Capper
- Department of Neuropathology, University Heidelberg, Heidelberg
| Veröffentlicht: | 13. Mai 2014 |
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Gliederung
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Objective: Neuroepithelial tumors are a frequent cause of intractable epilepsy. For gangliogliomas associations between BRAF V600E mutation status and reduced recurrence free survival has recently been described. We here investigate a large series of (long-term) epilepsy-associated tumors of various histologies for BRAF V600E and IDH1 R132H mutations with a focus on epilepsy outcome.
Method: We identified 158 tumor patients (80.2% with pharmacoresistant epilepsy) who had epilepsy surgery between 1997 and 2012 with tissue available for immunohistochemical IDH1 R132H and BRAF V600E mutation analysis (clones H09 and VE1). Relevant clinical data and follow-up information were obtained from a prospectively maintained electronic database. Median follow-up was 65 months (range 1–372).
Results: The study cohort consisted of 132 typical longstanding epilepsy associated tumors [gangliogliomas (n=81), gangliocytomas (n=1), dysembryoplastic neuroepithelial tumors (DNT, n=32), pleomorphic xanthoastrocytomas (n=11), angiocentric gliomas (n=5), pilocytic astrocytomas (n=2)] as well as 26 diffuse gliomas WHO grade II and III. During the study period 5 (3.2%) patients died and 19 (12.0%) experienced tumor recurrence. BRAF V600E mutations were exclusively observed in gangliogliomas (32.1%), pleomorphic xanthoastrocytomas (45.5%) and in one diffuse glioma. IDH1 R132H mutations were observed in 42.3% of diffuse gliomas and in one ganglioglioma. Overall 70.9% of the patients were seizure free (ILAE1) at the last available follow-up. 70.6% of patients with recurrent seizures were also diagnosed with tumor recurrence (p=0.016). IDH1R 132H and BRAF V600E mutations were not associated with epilepsy outcomes. Recurrence free survival correlated strongly with histology (p<0.001) and extent of resection (p=0.004). Only gangliogliomas harbouring BRAF V600E mutations recurred during follow-up (p=0.063/NS). IDH1 R132H mutations were significantly correlated with a shorter recurrence free survival (p<0.0001) reflecting the strong association with diffuse glioma histology.
Conclusions: Histology is the most prominent predictor of epileptological and oncological outcomes after epilepsy surgery for typical LEATs and diffuse gliomas presenting with difficult or pharmacoresistant epilepsy. BRAFV600E mutation analysis distinguishes well between the various LEAT subtypes. IDH1 R132H mutations correlate strongly with diffuse glioma histology.
