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- Title
HDAC3 overexpression is an independent predictor of poor prognosis and is associated with genomic instability in prostate cancer.
- Authors
Krech, Till; Koop, Christina; Simon, Ronald; Steurer, Stefan; Sauter, Guido; Minner, Sarah; Wittmer, Corinna; Wilczak, Waldemar; Hinsch, Andrea; Lebok, Patrick; Heinzer, Hans; Graefen, Markus; Huland, Hartwig; Schlomm, Thorsten; Burdelski, Christoph
- Abstract
Objective: Histone deacetylases (HDACs) are modifiers of histone and non-histone proteins and play an important role in tumour development and progression. The current study aims to analyze prevalence and prognostic impact of HDAC3 in prostate cancer. Methods: HDAC3 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancer specimens. Results were compared to tumour phenotype, biochemical recurrence, and molecular subtypes defined by ERG status as well as genomic deletions of 3p, 5q, 6q and PTEN. Data and results: HDAC3 immunostaining was detectable in 75.5% of 9,643 interpretable cancers and considered strong in 15.5%, moderate in 33.1% and weak in 12.0% of cases. High HDAC3 expression was associated with high Gleason grade (p<0.0001), advanced pathological tumour stage (p<0.0001), positive nodal status (p<0.0001), elevated preoperative PSA-level (p<0.0001), positive surgical margin (p<0.0001), early PSA recurrence (p<0.0001) and increased cell proliferation p<0.0001). In subgroup analyses these associations were largely driven by ERG-negative cancers. High-level HDAC3 staining was also 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=0.0004) and 5q (p=0.0062) in ERG-negative cancers. The prognostic impact of HDAC3 was independent of established clinicopathological parameters when all prostate cancers were jointly analyzed. Conclusions: HDAC3 overexpression is an independent predictor of poor prognosis in prostate cancer with a possible role in the development of genetically instable and particularly aggressive tumours. Thus HDAC3 measurement might have potential for inclusion into clinical routine assays for risk assessment of prostate cancers.
- Publication
Canadian Journal of Pathology, 2016, Vol 8, p14
- ISSN
1918-915X
- Publication type
Article