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Expression of histone deacetylases 1,2 and 3 in urothelial bladder cancer


Poyet, Cédric; Jentsch, Bastian; Hermanns, Thomas; Schweckendiek, Daniel; Seifert, Hans-Helge; Schmidtpeter, Martin; Sulser, Tullio; Moch, Holger; Wild, Peter J; Kristiansen, Glen (2014). Expression of histone deacetylases 1,2 and 3 in urothelial bladder cancer. BMC Clinical Pathology, 14:10.

Abstract

BACKGROUND: Histone deacetylases (HDACs) are known to be associated with an overexpression in different types of cancer such as colon and prostate cancer. In this study we aimed to evaluate the protein expression of class I HDACs in urothelial carcinoma of the bladder.
METHODS: A tissue microarray containing 348 tissuesamples from 174 patients with a primary urothelial carcinoma of the bladder was immunohistochemically stained for (HDAC) 1, 2 and 3. Intensity of staining was evaluated and the association with clinico-pathological features and prognosis was assessed.
RESULTS: High HDAC expression levels were found in 40 to 60% of all investigated urothelial carcinomas (HDAC-1: 40%, HDAC-2: 42%, HDAC-3: 59%).HDAC-1 and HDAC-2 were significantly associated with higher tumour grades.Although all three markers could not predict progression in univariate analyses, high HDAC-1 expression was associated with a trend toward poorer prognosis. Patients with high-grade tumours and high expression levels of HDAC-1 were more likely to progress compared to all other patients (p < 0.05).
CONCLUSIONS: High-grade noninvasive papillary bladder tumours are associated with high expression levels of HDAC-1 and HDAC-2. High grade tumours in combination with high expression of HDAC-1 showed a worse prognosis than the other tumours. The high expression levels of HDACs observed particularly in high grade urothelial bladder cancer clearly warrant subsequent studies on the potential use of HDAC inhibitors as a novel therapeutic approach.

Abstract

BACKGROUND: Histone deacetylases (HDACs) are known to be associated with an overexpression in different types of cancer such as colon and prostate cancer. In this study we aimed to evaluate the protein expression of class I HDACs in urothelial carcinoma of the bladder.
METHODS: A tissue microarray containing 348 tissuesamples from 174 patients with a primary urothelial carcinoma of the bladder was immunohistochemically stained for (HDAC) 1, 2 and 3. Intensity of staining was evaluated and the association with clinico-pathological features and prognosis was assessed.
RESULTS: High HDAC expression levels were found in 40 to 60% of all investigated urothelial carcinomas (HDAC-1: 40%, HDAC-2: 42%, HDAC-3: 59%).HDAC-1 and HDAC-2 were significantly associated with higher tumour grades.Although all three markers could not predict progression in univariate analyses, high HDAC-1 expression was associated with a trend toward poorer prognosis. Patients with high-grade tumours and high expression levels of HDAC-1 were more likely to progress compared to all other patients (p < 0.05).
CONCLUSIONS: High-grade noninvasive papillary bladder tumours are associated with high expression levels of HDAC-1 and HDAC-2. High grade tumours in combination with high expression of HDAC-1 showed a worse prognosis than the other tumours. The high expression levels of HDACs observed particularly in high grade urothelial bladder cancer clearly warrant subsequent studies on the potential use of HDAC inhibitors as a novel therapeutic approach.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Urological Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2014
Deposited On:24 Mar 2014 14:00
Last Modified:08 Dec 2017 04:49
Publisher:BioMed Central
ISSN:1472-6890
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/1472-6890-14-10
PubMed ID:24624923

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