gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

FISH-, expression- and methylation analyses of p16 correlated with response to TMZ chemotherapy in patients with glioblastoma

FISH-, Expressions- und Methylierungsanalysen von p16 in Korrelation zum Ansprechverhalten auf Temozolomidchemotherapie bei Patienten mit Glioblastom

Meeting Abstract

  • corresponding author S. Alt - Institut für Humangenetik, Universitätskliniken des Saarlandes, Homburg/Saar
  • S. Wemmert - Klinik für Neurochirurgie, Universitätskliniken des Saarlandes, Homburg/Saar
  • R. Ketter - Klinik für Neurochirurgie, Universitätskliniken des Saarlandes, Homburg/Saar
  • A. von Deimling - Klinik für Neuropathologie, Universitätskliniken des Saarlandes, Homburg/Saar
  • W. I. Steudel - Klinik für Neurochirurgie, Universitätskliniken des Saarlandes, Homburg/Saar
  • S. Urbschat - Klinik für Neurochirurgie, Universitätskliniken des Saarlandes, Homburg/Saar

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocP 071

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc326.shtml

Veröffentlicht: 11. April 2007

© 2007 Alt 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: The clinical course of glioblastomas is mainly determined by the biological behavior of the tumor cells and their response to radiation and chemotherapy because a surgical cure is virtually impossible. Temozolomid (TMZ), a second-generation imidazotetrazine, increase the median survival time of patients with glioblastomas, especially those with deletions of the short arm of chromosome 9. The aim of our study was to investigate whether the tumor suppressor gene CDKN2A/p16 on 9p is responsible for the positive effect of TMZ of the survival time of patients with glioblastomas.

Methods: To investigate the deletions of CDKN2A on DNA level, we used two-color FISH with a centromere specific probe of chromosome 9 in combination with a gene specific probe for CDKN2A on paraffin embedded tissues. In order to correlate this with the loss of p16 on protein level, we performed immunohistochemical analyses with a specific antibody against p16. The possible inactivation of CDKN2A by hypermethylation of the promotor was analysed by methylation specific PCR.

Results: By FISH we found 8/19 cases with homozygous deletion of CDKN2A while 10/19 cases showed a heterozygous deletion of the gene. Patients with homozygous deletions had a decreased survival time (9.2 months) in contrast to patients with heterozygous deletions (20.4 months). The immunohistochemistry was performed on 20 paraffin embedded tissues of glioblastomas. Patients treated with TMZ chemotherapy showed an increased survival time in univariate analysis when they express p16 (p=0,06). In the same way patients with cytoplasmic expression of p16 had an increased survival time in contrast to patients who express p16 in the cell nucleus. The methylation specific PCR revealed an inactivation of CDKN2A by promotor hypermethylation in 5/45 cases.

Conclusions: This study demonstrates that the loss of CDKN2A/p16 might be correlated with a worse prognosis. However, these patients seem to respond to TMZ chemotherapy in an increased survival time. Further on, patients who still express p16 showed evidence for an increased survival time, especially when they express p16 mainly in the cytoplasm.