title: Hematogenous dissemination of glioblastoma multiforme.
abstract: Glioblastoma multiforme (GBM) is the most frequent and aggressive brain tumor in adults. The dogma that GBM spread is restricted to the brain was challenged by reports on extracranial metastases after organ transplantation from GBM donors. We identified circulating tumor cells (CTCs) in peripheral blood (PB) from 29 of 141 (20.6%) GBM patients by immunostaining of enriched mononuclear cells with antibodies directed against glial fibrillary acidic protein (GFAP). Tumor cell spread was not significantly enhanced by surgical intervention. The tumor nature of GFAP-positive cells was supported by the absence of those cells in healthy volunteers and the presence of tumor-specific aberrations such as EGFR gene amplification and gains and losses in genomic regions of chromosomes 7 and 10. Release of CTCs was associated with EGFR gene amplification, suggesting a growth potential of these cells. We demonstrate that hematogenous GBM spread is an intrinsic feature of GBM biology.
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, D-201246 Hamburg, Germany.
authors: Carolin
authors: C
authors: Müller
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, D-201246 Hamburg, Germany. Klinik für Senologie, Kliniken Essen-Mitte, D-45136 Essen, Germany.
authors: Johannes
authors: J
authors: Holtschmidt
authors: Institute of Human Genetics, Medical University of Graz, A-8010 Graz, Austria.
authors: Martina
authors: M
authors: Auer
authors: Institute of Human Genetics, Medical University of Graz, A-8010 Graz, Austria.
authors: Ellen
authors: E
authors: Heitzer
authors: Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
authors: Katrin
authors: K
authors: Lamszus
authors: Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
authors: Alexander
authors: A
authors: Schulte
authors: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
authors: Jakob
authors: J
authors: Matschke
authors: Institute of Human Genetics, Technical University of Munich, D-81675 Munich, Germany.
authors: Sabine
authors: S
authors: Langer-Freitag
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, D-201246 Hamburg, Germany.
authors: Christin
authors: C
authors: Gasch
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, D-201246 Hamburg, Germany.
authors: Malgorzata
authors: M
authors: Stoupiec
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, D-201246 Hamburg, Germany.
authors: Oliver
authors: O
authors: Mauermann
authors: Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
authors: Sven
authors: S
authors: Peine
authors: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
authors: Markus
authors: M
authors: Glatzel
authors: Institute of Human Genetics, Medical University of Graz, A-8010 Graz, Austria.
authors: Michael R
authors: MR
authors: Speicher
authors: Institute of Human Genetics, Medical University of Graz, A-8010 Graz, Austria.
authors: Jochen B
authors: JB
authors: Geigl
authors: Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
authors: Manfred
authors: M
authors: Westphal
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, D-201246 Hamburg, Germany. pantel@uke.de.
authors: Klaus
authors: K
authors: Pantel
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, D-201246 Hamburg, Germany.
authors: Sabine
authors: S
authors: Riethdorf
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002879:Chromosomes, Human, Pair 10; D002897:Chromosomes, Human, Pair 7; D055028:Comparative Genomic Hybridization; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics / Q000556:secondary* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; C512478:EGFR protein, human; D066246:ErbB Receptors