title: Overexpression of the chromatin remodeler death-domain-associated protein in prostate cancer is an independent predictor of early prostate-specific antigen recurrence.
abstract: Molecular markers reliably predicting the aggressiveness of prostate cancer are currently lacking. Death-domain-associated protein (DAXX) has been implicated in the regulation of chromatin remodeling, transcription, and apoptosis that are integral to oncogenesis and cancer progression. DAXX expression was analyzed by immunohistochemistry on a tissue microarray containing 7478 prostate cancer specimens. Results were compared with tumor phenotype, biochemical recurrence, and v-ets erythroblastosis virus E26 oncogene homolog (ERG) status. DAXX expression was predominantly seen in the nucleus. DAXX expression was detectable in 4609 (80.6%) of 5718 interpretable cancers and considered strong in 5.9%, moderate in 45.8%, and weak in 28.9%. Strong DAXX expression was associated with both transmembrane protease, serine 2 (TMPRSS2)/ERG rearrangement and ERG expression (P < .0001 each). Strong DAXX expression was tightly linked to high Gleason grade, advanced pT stage, increased cell proliferation index, and early prostate-specific antigen recurrence (P < .0001 each). The prognostic role of DAXX expression was independent of Gleason grade, pT stage, and pN stage. Our study establishes DAXX as a novel independent prognosticator in prostate cancer and suggests an important role of DAXX expression for both prostate cancer development and progression. Furthermore, DAXX appears to exert biologically different effects in ERG-positive and ERG-negative prostate cancers.
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.
authors: Maria Christina
authors: MC
authors: Tsourlakis
authors: Michael
authors: M
authors: Schoop
authors: Christoph
authors: C
authors: Plass
authors: Hartwig
authors: H
authors: Huland
authors: Markus
authors: M
authors: Graefen
authors: Thomas
authors: T
authors: Steuber
authors: Thorsten
authors: T
authors: Schlomm
authors: Ronald
authors: R
authors: Simon
authors: Guido
authors: G
authors: Sauter
authors: Hüseyin
authors: H
authors: Sirma
authors: Sarah
authors: S
authors: Minner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D056970:Co-Repressor Proteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C072312:ERG protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D017430:Prostate-Specific Antigen
keywords: DAXX; Prostate cancer; TMPRSS2/ERG