title: Proteomic identification of glutamine synthetase as a differential marker for oligodendrogliomas and astrocytomas.
abstract: OBJECTIVE
  Astrocytomas and oligodendrogliomas are primary CNS tumors that remain a challenge to differentiate histologically because of their morphological variability and because there is a lack of reliable differential diagnostic markers. To identify proteins that are differentially expressed between astrocytomas and oligodendrogliomas, the authors analyzed the proteomic expression patterns and identified uniquely expressed proteins in these neoplasms.
  
  
  METHODS
  Proteomes of astrocytomas and oligodendrogliomas were analyzed using 2D gel electrophoresis and subsequent computerized gel analysis to detect differentially expressed proteins. The proteins were identified using high-performance liquid chromatography accompanied by tandem mass spectrometry. To determine the role of the differentially expressed proteins in astrocytes, undifferentiated glial cell cultures were treated with dibutyryl-cyclic adenosine monophosphate (cAMP).
  
  
  RESULTS
  Two-dimensional gel electrophoresis revealed that glutamine synthetase was differentially expressed in astrocytomas and oligodendrogliomas. Western blot and immunohistochemical analyses confirmed the increased expression of glutamine synthetase in astrocytomas compared with oligodendrogliomas. Whereas glutamine synthetase expression was demonstrated across all grades of astrocytomas (Grade II-IV [15 tumors]) and oligoastrocytomas (4 tumors), it was expressed in only 1 oligodendroglioma (6% [16 tumors]). Treatment of undifferentiated glial cell cultures with dibutyryl-cAMP resulted in astrocyte differentiation that was associated with increased levels of glial fibrillary acidic protein and glutamine synthetase.
  
  
  CONCLUSIONS
  These data indicate that glutamine synthetase expression can be used to distinguish astrocytic from oligodendroglial tumors and may play a role in the pathogenesis of astrocytomas.
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA. zhuangp@ninds.nih.gov
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Meng
authors.initials: M
authors.lastname: Qi
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.forename: David S
authors.initials: DS
authors.lastname: Xu
authors.forename: Rajiv R
authors.initials: RR
authors.lastname: Iyer
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Chunzhang
authors.initials: C
authors.lastname: Yang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Weil
authors.forename: Alexander
authors.initials: A
authors.lastname: Vortmeyer
authors.forename: Russell R
authors.initials: RR
authors.lastname: Lonser
mesh_terms: D001254:Astrocytoma / Q000175:diagnosis* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006801:Humans; D009837:Oligodendroglioma / Q000175:diagnosis* / Q000378:metabolism; D040901:Proteomics
chemical_list: D014408:Biomarkers, Tumor; D005974:Glutamate-Ammonia Ligase