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Prognostic factors in malignant glioma: Influence of the overexpression of oncogene and tumor-suppressor gene products on survival

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Abstract

Despite the use of multimodal therapy, higher-grade glioma is stilluniformly fatal in the adult population. There is a considerable differencebetween the length of survival in each given patient, even within the sametumor type and malignancy grade group, suggesting that there are factorsthat might differentially influence outcome. To identify such factors, 107patients with anaplastic or malignant glioma were retrospectivelyinvestigated. Clinical parameters and paraclinical data on the p53, mdm2,and EGFR genes at the DNA or protein level were evaluated by univariateanalysis and Cox proportional hazards regression modeling. Kaplan-Meiersurvival estimation demonstrated that immunohistochemical positivity formdm2 protein in patients with anaplastic astrocytoma or with glioblastomamultiforme was associated with a shorter survival time (p = 0.02).P53 gene mutations and immunopositivity for the epidermal growth factorreceptor (EGFR) protein were not significantly related to poor prognosis.The Cox proportional hazards model revealed immunohistochemical positivityfor p53, mdm2, or for both of them, the presence of postoperativeirradiation, and the extent of surgical resection of tumor to be variablessignificantly associated with prolonged survival. EGFR overexpression, ageover 60 years, and Karnofsky performance score below 40 points did notsignificantly shorten survival time. In conclusion, the present studyidentified immunohistochemically detected mdm2-protein overexpression as astatistically significant negative prognostic parameter in patients bearinganaplastic or malignant glioma. Association analysis of variables revealed apossible correlation between mdm2 and p53, which is also consistent with thebiological interaction mode of both proteins in vivo.

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Authors and Affiliations

  1. Department of Neurosurgery, Faculty of Medicine, Martin-Luther-University, Halle-Wittenberg, Germany

    Nikolai G. Rainov, Karl-Ulrich Dobberstein, Volkmar Heidecke & Winfried Burkert

  2. Institute of Pathology, Faculty of Medicine, Martin-Luther-University, Halle-Wittenberg, Germany

    Hannes Bahn & Hans-Jürgen Holzhausen

  3. Institute of Medical Informatics and Biostatistics, Faculty of Medicine, Martin-Luther-University, Halle-Wittenberg, Germany

    Christine Lautenschläger

Authors
  1. Nikolai G. Rainov
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  2. Karl-Ulrich Dobberstein
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  3. Hannes Bahn
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  4. Hans-Jürgen Holzhausen
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  5. Christine Lautenschläger
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  6. Volkmar Heidecke
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  7. Winfried Burkert
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Rainov, N.G., Dobberstein, KU., Bahn, H. et al. Prognostic factors in malignant glioma: Influence of the overexpression of oncogene and tumor-suppressor gene products on survival. J Neurooncol 35, 13–28 (1997). https://doi.org/10.1023/A:1005841520514

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  • DOI: https://doi.org/10.1023/A:1005841520514

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