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 and p15 promotor methylation – prognostic parameters for TMZ chemotherapy response?

MGMT und p15 Promotor-Methylierung – prognostische Parameter für ein Ansprechen auf TMZ-Chemotherapie?

Meeting Abstract

  • corresponding author R. Ketter - Neurochirurgische Klinik, Universität des Saarlandes, Homburg/Saar
  • S. Wemmert - Neurochirurgische Klinik, Universität des Saarlandes, Homburg/Saar
  • M. Bettscheider - Neurochirurgische Klinik, Universität des Saarlandes, Homburg/Saar
  • S. Alt - Neurochirurgische Klinik, Universität des Saarlandes, Homburg/Saar
  • W. I. Steudel - Neurochirurgische Klinik, Universität des Saarlandes, Homburg/Saar
  • S. Urbschat - Neurochirurgische Klinik, Universität des Saarlandes, Homburg/Saar

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.13.05

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2008/08dgnc128.shtml

Veröffentlicht: 30. Mai 2008

© 2008 Ketter 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

Text

Objective: Glioblastomas are the most frequent and malignant tumors of the central nervous system. Surgical cure is virtually impossible and the clinical course is mainly determined by the biological behaviour of the tumor cells and their response to radiation and chemotherapy. MGMT promotor hypermethylation was shown to be a prognostic parameter for TMZ response. We were also able to show that TMZ increases the median survival time of patients with tumors harbouring deletions on 9p with the loci for CDKN2A (p16, p14ARF) and CDKN2B (p15). Therefore, the aim of our current study was to investigate the role of the methylation status of p15, p16 and p14ARF in addition to MGMT methylation status and correlate these results with the clinical data.

Methods: DNA was isolated from fresh frozen GBM biopsies (n=22), and modified by sodium bisulfite. Methylation-specific polymerase chain reaction (MS-PCR) was performed to analyze the methylation status of MGMT, p15, p16 and p14ARF and the results were correlated to the overall survival time. All patients were treated with radiotherapy and TMZ chemotherapy after radical tumor resection. Only patients with a good Karnofsky Score (>70) were included.

Results: We observed methylation of the MGMT promotor in 59% (13/22) and of p15 in 32% (7/22) of the tumors, whereas methylation of p16 and p14arf plays no important role in these tumors (5% and 0%, respectively). Overall survival time of patients with methylated MGMT was 26 months compared to 22 months of patients with unmethylated MGMT. Interestingly, patients with methylated p15 showed a drastic decrease in survival time compared to unmethylated p15 (16 vs. 30 months). Patients harbouring methylation of p15 and MGMT had a survival time comparable of those with only methylated p15, whereas patients with a methylated MGMT and unmethylated p15 showed the best prognosis under TMZ (33 months).

Conclusions: Our retrospective study showed that patients with tumors exhibiting methylated MGMT and unmethylated p15 benefit most from TMZ therapy, whereas the methylation of p15 might act as an marker for a poorer clinical course.