gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Distinct chromosomal and microsatellite instability profiles in giant-cell glioblastoma multiforme compared to standard glioblastoma

Unterschiedliches molekulargenetisches Profil von Riesenzell-GBMs im Vergleich zu Standard-GBMs

Meeting Abstract

  • corresponding author Ramon Martinez - Neurochirurgische Klinik, Universität Dresden, Dresden
  • H. K. Schackert - Abteilung Chirurgische Forschung, Universität Dresden, Dresden
  • R. Klein - Institut für Neuropathologie, Universität Würzburg, Würzburg
  • W. Roggendorf - Institut für Neuropathologie, Universität Würzburg, Würzburg
  • G. Schackert - Neurochirurgische Klinik, Universität Dresden, Dresden

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocP 04.34

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2004/04dgnc0317.shtml

Published: April 23, 2004

© 2004 Martinez et al.
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Outline

Text

Objective

Giant cell glioblastoma (gcGBM) is a peculiar variant of glioblastoma multiforme (GBM) characterized by a preponderance of multinucleated giant cells. Compared to ordinary glioblastoma it shows a distinct clinicopathological and molecular profile. The mechanisms implicated in genomic instability have not been yet described in gcGBM.

Methods

We analyzed the mutational spectrum of p53 and PTEN, analyzed EGFR amplification as well as microsatellite instability (MSI) and mismatch repair (MMR) protein expression in 14 gcGBM in order to assess genomic instability and compared it with 52 standard GBMs. Student´s t-test was performed to investigate immunohistochemical protein densitometry. Two-tailed Fisher´s exact test was used to analyze the significance of p53, EGFR and PTEN. Odds ratios and 95% confidence intervals were obtained through logistic regression.

Results

Multiple p53 mutations affecting single specimens were frequently observed (11 out of 14 samples, 78.6%, P<0.05), including a remarkably high rate of acceptor site splice mutations in 6 gcGBMs compared to standard glioblastomas (P<0.05). Low-level MSI was more frequent in gcGBM compared to common GBMs (28.6% vs. 8.5%, P<0.05). A deficient expression of the MMR proteins MLH1 and PMS2 was observed in the giant-cell phenotype of two MSI(+) tumors. PTEN was mutated in all gcGBM except in those showing MSI.

Conclusions

These results strongly suggest that gcGBM differs from ordinary GBM in the rate and pattern of both chromosomal and microsatellite instability, which might contribute to explain the distinct clinicopathological features of these tumors.