Abstract
BackgroundHistone 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.MethodsA 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.ResultsHigh 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).ConclusionsHigh-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.
Highlights
Histone deacetylases (HDACs) are known to be associated with an overexpression in different types of cancer such as colon and prostate cancer
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)
Summary
Histone deacetylases (HDACs) are known to be associated with an overexpression in different types of cancer such as colon and prostate cancer. The majority of bladder cancer patients (75-80%) initially present with papillary noninvasive (pTa) or superficially invasive (pT1) urothelial carcinoma, whereas the remaining 20-25% of primary tumours are already muscle invasive (≥ pT2) at first diagnosis [1,2]. Bladder cancer patients have to be monitored closely for disease recurrence and progression, which contributes to the high costs †. Histone deacetylases (HDACs) constitute a family of enzymes that deacetylate histones and other cellular proteins. They are major regulators of transcription and are important in other cellular processes [5].
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