gms | German Medical Science

59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

01. - 04.06.2008, Würzburg

MGMT promoter hypermethylation does not correlate with MGMT protein expression in malignant gliomas

MGMT Promotor-Hypermethylierung korreliert nicht mit der MGMT Protein-Expression in malignen Gliomen

Meeting Abstract

  • corresponding author O. Schnell - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität München
  • E. Grasbon-Frodl - Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität München
  • G. Reifenberger - Institut für Neuropathologie, Klinikum der Heinrich-Heine-Universität, Düsseldorf
  • H. Kretzschmar - Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität München
  • J.-C. Tonn - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität München
  • F. W. Kreth - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität München

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocMO.13.04

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2008/08dgnc127.shtml

Veröffentlicht: 30. Mai 2008

© 2008 Schnell et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Objective: Intratumoral homogeneity of MGMT promoter methylation in malignant gliomas has been demonstrated by use of stereotactic serial biopsy. Whereas MGMT promoter methylation has been linked to a survival benefit for glioblastoma patients receiving concomitant radio-chemotherapy, there are uncertainties according to its correlation with MGMT protein expression. The aim of our study was to assess MGMT protein expression compared to MGMT promoter methylation in malignant gliomas from small sized stereotactic biopsy samples.

Methods: Specimens (1mm3) from adult patients (n=25) with supratentorial malignant gliomas were obtained by stereotactic serial biopsy from different sites within each glioma. MGMT promoter methylation was analyzed via methylation specific PCR and sequencing analysis. MGMT protein expression was analyzed by immunohistochemistry of adjacent samples (level±1mm). The fraction of MGMT-positive tumor cells in each sample was evaluated semiquantitatively and dichotomized thereafter: a low MGMT protein expression was assumed in case of <10% immuno-positive tumor cells; otherwise protein expression was classified as high (>10%).

Results: The overall MGMT promoter methylation rate was 40% in patients with malignant gliomas. MGMT immunohistochemistry could be performed in 23 tumors and revealed a homogenous expression pattern throughout each tumor. As expected, a high MGMT protein expression (≥10% positive tumor cells) was seen in 9 unmethylated and a low expression in 4 methylated tumors. However, 4 unmethylated tumors showed a low fraction (<10%) and 6 patients with a methylated MGMT promoter a high fraction of immuno-positive tumor (>10%). No correlation was found between the MGMT promoter methylation status and the fraction of MGMT protein positive tumor cells.

Conclusions: The intratumoral distribution of both, the MGMT promoter methylation and the degree of MGMT protein expression is homogenous in malignant gliomas and can therefore be obtained reliably from small sized biopsy specimens. The lack of correlation between MGMT promoter methylation and MGMT protein expression needs further evaluation. So far unknown control mechanisms at the transcriptional, posttranscriptional and/or translational level may exist.