title: Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy.
abstract: High activity of histone deacetylases (HDACs) causes epigenetic alterations associated with malignant cell behaviour. Consequently, HDAC inhibitors have entered late-phase clinical trials as new antineoplastic drugs. However, little is known about expression and function of specific HDAC isoforms in human tumours including prostate cancer. We investigated the expression of class I HDACs in 192 prostate carcinomas by immunohistochemistry and correlated our findings to clinicopathological parameters including follow-up data. Class I HDAC isoforms were strongly expressed in the majority of the cases (HDAC1: 69.8%, HDAC2: 74%, HDAC3: 94.8%). High rates of HDAC1 and HDAC2 expression were significantly associated with tumour dedifferentiation. Strong expression of all HDACs was accompanied by enhanced tumour cell proliferation. In addition, HDAC2 was an independent prognostic marker in our prostate cancer cohort. In conclusion, we showed that the known effects of HDACs on differentiation and proliferation of cancer cells observed in vitro can also be confirmed in vivo. The class I HDAC isoforms 1, 2 and 3 are differentially expressed in prostate cancer, which might be important for upcoming studies on HDAC inhibitors in this tumour entity. Also, the highly significant prognostic value of HDAC2 clearly deserves further study.
authors.affiliation: Institute of Pathology, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Weichert
authors.forename: A
authors.initials: A
authors.lastname: Röske
authors.forename: V
authors.initials: V
authors.lastname: Gekeler
authors.forename: T
authors.initials: T
authors.lastname: Beckers
authors.forename: C
authors.initials: C
authors.lastname: Stephan
authors.forename: K
authors.initials: K
authors.lastname: Jung
authors.forename: F R
authors.initials: FR
authors.lastname: Fritzsche
authors.forename: S
authors.initials: S
authors.lastname: Niesporek
authors.forename: C
authors.initials: C
authors.lastname: Denkert
authors.forename: M
authors.initials: M
authors.lastname: Dietel
authors.forename: G
authors.initials: G
authors.lastname: Kristiansen
mesh_terms: D000368:Aged; D015331:Cohort Studies; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000032:analysis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000201:enzymology*; D012097:Repressor Proteins / Q000378:metabolism; D016019:Survival Analysis; D000099186:Histone Deacetylase 3
chemical_list: D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D017430:Prostate-Specific Antigen; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C110550:HDAC1 protein, human