title: Overexpression of ADK in human astrocytic tumors and peritumoral tissue is related to tumor-associated epilepsy.
abstract: OBJECTIVE
  Adenosine kinase (ADK), a largely astrocyte-based metabolic enzyme, regulates adenosine homeostasis in the brain. Overexpression of ADK decreases extracellular adenosine and consequently leads to seizures. We hypothesized that dysfunction in the metabolism of tumor astrocytes is related to changes in ADK expression and that those changes might be associated with the development of epilepsy in patients with tumors.
  
  
  METHODS
  We compared ADK expression and cellular distribution in surgically removed tumor tissue (n = 45) and peritumoral cortex (n = 20) of patients with glial and glioneuronal tumors to normal control tissue obtained at autopsy (n = 11). In addition, we compared ADK expression in tumor patients with and without epilepsy. To investigate ADK expression, we used immunohistochemistry and Western blot analysis. ADK activity measurement was performed in surgical specimens of astrocytomas World Health Organization (WHO) grade III (n = 3), peritumoral cortex (n = 3), and nonepileptic cortex (n = 3).
  
  
  RESULTS
  Immunohistochemistry predominantly showed cytoplasmic labeling in tumors and peritumoral tissue containing infiltrating tumor cells. ADK immunoreactivity was significantly stronger in tumor and peritumoral tissue compared to normal white matter and normal cortex, especially in astrocytoma WHO grade III, as confirmed by Western blot analysis and ADK activity measurements. Importantly, we found a significantly higher expression of ADK in the peritumoral infiltrated tissue of patients with epilepsy than in patients without epilepsy.
  
  
  CONCLUSIONS
  These results suggest a dysregulation of ADK in astrocytic brain tumors. Moreover, the upregulation of ADK observed in peritumoral infiltrated tissue of glioma patients with epilepsy supports the role of this enzyme in tumor-associated epilepsy.
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: de Groot
authors.forename: Anand
authors.initials: A
authors.lastname: Iyer
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zurolo
authors.forename: Jasper
authors.initials: J
authors.lastname: Anink
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Heimans
authors.forename: Detlev
authors.initials: D
authors.lastname: Boison
authors.forename: Jaap C
authors.initials: JC
authors.lastname: Reijneveld
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
mesh_terms: D000248:Adenosine Kinase / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism*; D002648:Child; D004827:Epilepsy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000248:Adenosine Kinase
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