gms | German Medical Science

62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

Unfavourable prognostic influence of IDH1 mutations in WHO Grade II astrocytomas turns into favourable predictive impact after malignant transformation

Meeting Abstract

  • N. Thon - Neurochirurgische Klinik, Klinikum Großhadern, Ludwig Maximilians-Universität München
  • S. Eigenbrod - Institut für Neuropathologie und Prion Erkrankung, Klinikum Großhadern, Ludwig Maximilians-Universität München
  • S. Kreth - Klinik für Anaesthesiologie, Klinikum Großhadern, Ludwig Maximilians-Universität München
  • J. Lutz - Abteilung für Klinische Radiologie, Klinikum Großhadern, Ludwig Maximilians-Universität München
  • J.-C. Tonn - Neurochirurgische Klinik, Klinikum Großhadern, Ludwig Maximilians-Universität München
  • H. Kretzschmar - Institut für Neuropathologie und Prion Erkrankung, Klinikum Großhadern, Ludwig Maximilians-Universität München
  • A. Peraud - Neurochirurgische Klinik, Klinikum Großhadern, Ludwig Maximilians-Universität München
  • F.-W. Kreth - Neurochirurgische Klinik, Klinikum Großhadern, Ludwig Maximilians-Universität München

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMI.05.03

DOI: 10.3205/11dgnc212, URN: urn:nbn:de:0183-11dgnc2129

Published: April 28, 2011

© 2011 Thon et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: The favourable impact of isocitrate dehydrogenases 1 (IDH1) mutations is well documented for malignant gliomas. Its influence on WHO grade II gliomas, however, remains unclear.

Methods: IDH1 codon 132 pyrosequencing was performed in a mainly surgically treated series of 159 adult patients (1991–1998) harbouring WHO grade II gliomas (24 oligoastrocytomas). In addition MGMT promoter methylation was assessed by methylation-specific polymerase-chain reaction (MSP) and bisulfite sequencing. TP53 mutations were determined by sequencing analysis. Endpoints were overall survival (OS), progression-free survival (PFS), time to malignant transformation and post-recurrence survival (PRS).

Results: IDH1 mutations, TP53 mutations, and methylated MGMT promoters were seen in 77.9%, 45.9%, and 82.8% of analyzed tumors, respectively. The IDH1 mutation was strongly associated with both TP53 mutation and MGMT promoter methylation (p<0.001). IDH1 mutations correlated with shortened PFS (median 49 vs 84 months; p=0.003) but prolonged PRS after malignant transformation and subsequently applied radiotherapy (median: 24 vs. 8 months; p=0.01). A similar pattern of influence was seen for MGMT promoter methylation: methylated tumors did worse in terms of PFS and time to malignant transformation (p>0.05). In contrast, PRS was improved after malignant transformation (p<0.05). This analysis, however, was limited by a low number of unmethylated tumors. Conversely, TP53 mutations were stringently associated with a worse prognosis throughout the course of the disease.

Conclusions: The IDH1 mutation exhibits Janus Head-like properties: Its unfavourable prognostic influence on PFS turns into a favourable predictive impact after malignant transformation. A similar pattern of influence might exist for MGMT methylation.