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TP53 Gene Mutations, Nuclear p53 Accumulation, Expression of Waf/p21, Bcl-2, and CD95 (APO-1/Fas) Proteins are not Prognostic Factors in De Novo Glioblastoma Multiforme

Authors
  • Kraus, Jürgen A.1
  • Wenghoefer, Matthias1
  • Glesmann, Nicole1
  • Mohr, Svenja1
  • Beck, Martina1
  • Schmidt, Matthias C.2
  • Schröder, Rolf1
  • Berweiler, Ute3
  • Roggendorf, Wolfgang4
  • Diete, Sabine5
  • Dietzmann, Knut6
  • Heuser, Karlheinz7
  • Müller, Bettina8
  • Fimmers, Rolf9
  • von Deimling, Andreas10
  • Schlegel, Uwe1
  • 1 University of Bonn, Department of Neurology, Bonn , Bonn
  • 2 University of Bonn, Department of Neurosurgery, Bonn , Bonn
  • 3 University of Würzburg, Department of Neurosurgery, Würzburg , Würzburg
  • 4 University of Würzburg, Department of Neuropathology, Würzburg , Würzburg
  • 5 University of Madgeburg, Department of Neurology, Magdeburg , Magdeburg
  • 6 University of Madgeburg, Department of Neuropathology, Magdeburg , Magdeburg
  • 7 University of Kiel, Department of Neurology, Kiel , Kiel
  • 8 Bavaria Clinics, Department of Neurology, Kreischa, Germany , Kreischa
  • 9 University of Bonn, Department of Biostatistics, Bonn , Bonn
  • 10 Humboldt University of Berlin, Department of Neuropathology, Berlin, Germany , Berlin
Type
Published Article
Journal
Journal of Neuro-Oncology
Publisher
Springer-Verlag
Publication Date
May 01, 2001
Volume
52
Issue
3
Pages
263–272
Identifiers
DOI: 10.1023/A:1010684203704
Source
Springer Nature
Keywords
License
Yellow

Abstract

Glioblastoma multiforme (WHO grade IV; GBM) is the most common primary brain tumor with a median survival of less than one year despite multimodal treatment regimens. However, a small subgroup of GBM patients has a better clinical outcome, with a small number of patients surviving several years. Apoptosis, a genetically determined program of cell suicide, may be induced as a consequence of critical DNA damage. However, due to defects in the signaling pathways, cancer cells may escape apoptosis, despite carrying irreversible DNA damage. In the present study, we have analyzed tumors of two age-matched, equally treated groups of GBM patients with different postoperative time to tumor progression (TTP), defined as ‘short-term’ for TTP of less than 6 months (n = 54), and ‘long-term’ for TTP of more than 12 months (n = 39) for alterations in apoptosis regulatory pathways: Mutations of the TP53 tumor suppressor gene and/or nuclear accumulation of its gene product p53, expression of Waf/p21, CD95 (Apo1/Fas), and Bcl-2. TP53 mutations were found in 12 out of 54 (22%) GBMs of short-term survivors and 8 out of 35 (23%) tumors of long-term survivors; the respective numbers for nuclear p53 protein accumulation were 12/53 (23%) and 10/37 (27%). Waf1/p21 expression was found in 13/53 (25%) tumors of short-term survivors and 9/35 (26%) GBMs of long-term survivors. The respective numbers for Bcl-2 expression were 25/42 (60%) and 22/36 (61%) and for CD95 (Apo1/Fas) expression 20/49 (41%) and 14/36 (39%) GBMs. The percentage of alterations in genes/proteins involved in the apoptotic pathway investigated here was virtually identical in the two groups of clinically different GBM patients. Thus, our data imply that none of these alterations investigated per se has a strong impact on the overall survival of GBM patients.

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