title: DJ-1 expression in glioblastomas shows positive correlation with p53 expression and negative correlation with epidermal growth factor receptor amplification.
abstract: DJ-1, a protein that promotes the action of multiple anti-apoptotic/pro-survival pathways, is expressed prominently in human reactive astrocytes and in many human cancers. Glioblastomas (GBMs) are the most common adult primary brain tumor, and most show either abnormalities in p53 or epidermal growth factor receptor (EGFR) amplification, but not both. In this retrospective study of 40 surgically resected GBMs, we compared the immunohistochemical intensity of DJ-1 expression (based on blinded scoring by independent examiners) to these and other molecular factors associated with GBM oncogenesis. We report here that: (i) most of the GBMs that we studied expressed DJ-1 protein at significant levels, and typically in a cytoplasmic, non-nuclear fashion; (ii) DJ-1 staining intensity varied directly with strong nuclear p53 expression (assessed by immunostaining); and (iii) DJ-1 staining intensity varied inversely with EGFR amplification (assessed by fluorescent in situ hybridization). Since the anti-apoptotic/pro-survival actions of DJ-1 have been clearly linked in in vitro systems to p53 and receptor tyrosine kinase (i.e. EGFR) pathways that are hypothesized to be critical to GBM genesis, these observations indicate that DJ-1 expression may play a role in the biology of some types of GBMs. Therefore, given the new associations presented here between DJ-1, p53 and EGFR amplification in GBMs, future investigations of these tumors should include an analysis of DJ-1 to determine whether its expression pattern is important for tumor progression, prognosis and responsiveness to therapy.
authors.affiliation: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA. hinkleda@upmc.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Hinkle
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Mullett
authors.forename: Bethann E
authors.initials: BE
authors.lastname: Gabris
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hamilton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000096:biosynthesis*; D000071617:Protein Deglycase DJ-1; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1