title: Expression of WW domain-containing oxidoreductase WOX1 in human nervous system tumors.
abstract: OBJECTIVE
  We aimed to evaluate the expression levels of the tumor suppressor WOX1 in nervous system tumors and its co-expression with p53 and neurofibromatosis type 2/merlin (NF2) tumor suppressor gene products.
  
  
  METHODS
  Immunohistochemistry, western blotting and in situ hybridization were used for WOX1 protein and WWOX mRNA expression. Immunofluorescence and electron microscopical immunohistochemistry were performed for colocalization of gene products.
  
  
  RESULTS
  WOX1 expression is low in normal cortical neurons, mainly on the axon fibers, whereas there is moderate to high immunoreactivity in the cytosol and nuclei of certain tumor cells. In the microcystic (WHO grade I) and malignant (WHO grade III) meningiomas, WOX1 expression is intense, but various in transitional (WHO grade I) and atypical (WHO grade II) subtypes. WOX1 levels are moderate to high in the menigiotheliomatous area, but relatively low in the fibroblastic area. WOX1 and NF2/merlin, but not p53, colocalized in certain tumor cells, primarily at the borders of nuclei. Schwannoma and astrocytoma specimens stained moderately to strongly positive for the WOX1 protein. Interestingly, the expression of WOX1, NF2/merlin and mutant p53 is intense in high grade glioblastoma, but WOX1 expression is low in metastatic carcinoma or adenocarcinoma.
  
  
  CONCLUSIONS
  The expression of WOX1 on different types of nervous system tumors, including primary and metastatic tumors, is differential.
authors: Department of Neurosurgery, Mackay Memorial Hospital, Taipei, Taiwan Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, Taiwan.
authors: Ming-Fu
authors: MF
authors: Chiang
authors: Department of Cell Biology & Anatomy, Nation Cheng Kung University, Tainan, Taiwan.
authors: Shur-Tzu
authors: ST
authors: Chen
authors: Department of Cell Biology & Anatomy, Nation Cheng Kung University, Tainan, Taiwan.
authors: Chen-Peng
authors: CP
authors: Lo
authors: Department of Pathology, University of Colorado Health Sciences Center, Denver, CO, USA.
authors: Chun-I
authors: CI
authors: Sze
authors: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan Guthrie Research Institute, Laboratory of Molecular Immunology, Sayre, PA, USA Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
authors: Nan-Shan
authors: NS
authors: Chang
authors: Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan Graduate Institute of Pharmacology, Taipei Medical University, Taipei, Taiwan.
authors: Yu-Jen
authors: YJ
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008579:Meningioma / Q000378:metabolism; D008875:Middle Aged; D009423:Nervous System Neoplasms / Q000378:metabolism*; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D000074584:WW Domain-Containing Oxidoreductase; D055815:Young Adult
chemical_list: D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human
keywords: NF2/merlin; WOX1; brain tumors; meningioma; tumor suppressor gene