• Open Access

Cellular characterization of the peritumoral edema zone in malignant brain tumors

Authors

  • Tobias Engelhorn,

    1. Department of Neuroradiology, University of Erlangen-Nuremberg, Erlangen, Germany
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    • 8

      Both authors contributed equally to this work and are listed in alphabetical order.

  • Nic E. Savaskan,

    1. Brain Research Institute, Department of Biology, Swiss Institute of Technology (ETH) and University of Zurich, Zurich, Switzerland
    2. Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité-Universitätsmedizin Berlin, Berlin, Germany
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    • 8

      Both authors contributed equally to this work and are listed in alphabetical order.

  • Marc A. Schwarz,

    1. Department of Neurosurgery, University of Erlangen-Nuremberg, Erlangen, Germany
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  • Jürgen Kreutzer,

    1. Department of Neurosurgery, University of Erlangen-Nuremberg, Erlangen, Germany
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      Present address: Department of Neurosurgery, Technical University of Munich, Germany

  • Eric P. Meyer,

    1. Department of Zoology, University of Zurich, Zurich, Switzerland
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  • Eric Hahnen,

    1. Institute of Human Genetics, Institute of Genetics and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
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  • Oliver Ganslandt,

    1. Department of Neurosurgery, University of Erlangen-Nuremberg, Erlangen, Germany
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  • Arnd Dörfler,

    1. Department of Neuroradiology, University of Erlangen-Nuremberg, Erlangen, Germany
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  • Christopher Nimsky,

    1. Department of Neurosurgery, University of Erlangen-Nuremberg, Erlangen, Germany
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    • 10

      Present address: Department of Neurosurgery, University of Marburg, Germany

  • Michael Buchfelder,

    1. Department of Neurosurgery, University of Erlangen-Nuremberg, Erlangen, Germany
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  • Ilker Y. Eyüpoglu

    Corresponding author
    1. Department of Neurosurgery, University of Erlangen-Nuremberg, Erlangen, Germany
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To whom correspondence should be addressed. E-mail: eyupoglu@gmx.net or ilker.eyupoglu@uk-erlangen.de

Abstract

Brain edema is a hallmark of human malignant brain tumors and contributes to the clinical course and outcome of brain tumor patients. The so-called perifocal edema or brain swelling imposes in T2-weighted MR scans as high intensity areas surrounding the bulk tumor mass. The mechanisms of this increased fluid attraction and the cellular composition of the microenvironment are only partially understood. In this study, we focus on imaging perifocal edema in orthotopically implanted gliomas in rodents and correlate perifocal edema with immunohistochemical markers. We identified that areas of perifocal edema not only include the tumor invasion zone, but also are associated with increased glial fibrillary acidic protein (GFAP) and aquaporin-4 expression surrounding the bulk tumor mass. Moreover, a high number of activated microglial cells expressing CD11b and macrophage migration inhibitory factor (MIF) accumulate at the tumor border. Thus, the area of perifocal edema is mainly dominated by reactive changes of vital brain tissue. These data corroborate that perifocal edema identified in T2-weighted MR scans are characterized with alterations in glial cell distribution and marker expression forming an inflammatory tumor microenvironment. (Cancer Sci 2009; 100: 1856–1862)

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