title: HDAC1 overexpression independently predicts biochemical recurrence and is associated with rapid tumor cell proliferation and genomic instability in prostate cancer.
abstract: Histone deacetylases (HDACs) play an important role in tumor development and progression by modifying histone and non-histone proteins. In the current study we analyzed prevalence and prognostic impact of HDAC1 in prostate cancer. HDAC1 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancer specimens. Results were compared to tumor phenotype, biochemical recurrence, and molecular subtypes defined by ERG status as well as genomic deletions of 3p, 5q, 6q and PTEN. HDAC1 immunostaining was detectable in 75.4% of 9744 interpretable cancers and considered strong in 15.4%, moderate in 39.4% and weak in 20.7% of cases. High HDAC1 expression was associated with high Gleason grade (p<0.0001), advanced pathological tumor stage (p<0.0001), positive nodal status (p=0.0010), elevated preoperative PSA-level (p=0.0127), early PSA recurrence (p<0.0001) and increased cell proliferation (p<0.0001). Moreover, high-level HDAC1 staining was associated with TMPRSS2:ERG rearrangement and ERG expression in prostate cancers (p<0.0001) and was linked to deletions of PTEN (p<0.0001), 6q (p<0.0001) and 5q (p=0.0028) in ERG-negative cancers. The prognostic impact of HDAC1 was independent of established clinicopathological parameters and was mostly driven by ERG-negative cancers as revealed by subgroup analyses. HDAC1 has strong prognostic impact in prostate cancer and might contribute to the development of a fraction of genetically instable and particularly aggressive prostate cancers. HDAC1 measurement might therefore be of clinical value for risk stratification of prostate cancer and should be further evaluated in this regard.
authors: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany.
authors: Christoph
authors: C
authors: Burdelski
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Oliver M
authors: OM
authors: Ruge
authors: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany.
authors: Nathaniel
authors: N
authors: Melling
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Christina
authors: C
authors: Koop
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Ronald
authors: R
authors: Simon
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Stefan
authors: S
authors: Steurer
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Guido
authors: G
authors: Sauter
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Martina
authors: M
authors: Kluth
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Claudia
authors: C
authors: Hube-Magg
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Sarah
authors: S
authors: Minner
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Corinna
authors: C
authors: Wittmer
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Waldemar
authors: W
authors: Wilczak
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Andrea
authors: A
authors: Hinsch
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Patrick
authors: P
authors: Lebok
authors: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany.
authors: Jakob R
authors: JR
authors: Izbicki
authors: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors: Hans
authors: H
authors: Heinzer
authors: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors: Markus
authors: M
authors: Graefen
authors: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors: Hartwig
authors: H
authors: Huland
authors: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany; Department of Urology, Section for translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Germany.
authors: Thorsten
authors: T
authors: Schlomm
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany. Electronic address: t.krech@uke.de.
authors: Till
authors: T
authors: Krech
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D042822:Genomic Instability; D056284:Histone Deacetylase 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1
keywords: ERG; Genomic deletions; HDAC1; Immunohistochemistry; Prognosis; Prostate cancer; Tissue microarray