Research article
Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer
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* Corresponding author: Glen Kristiansen glen.kristiansen@usz.ch
- † Equal contributors
1 Institute of Pathology, Charité – Universitätsmedizin, Berlin, Germany
2 Department of Urology, Charité – Universitätsmedizin, Berlin, Germany
3 Nycomed GmbH, Konstanz, Germany
4 Oncotest GmbH, Freiburg, Germany
5 Berlin Institute for Urologic Research, Berlin, Germany
6 Institute of Surgical Pathology, UniversitätsSpital Zürich, Zurich, Switzerland
BMC Cancer 2008, 8:381 doi:10.1186/1471-2407-8-381
Published: 19 December 2008Abstract
Background
Enhanced activity of histone deacetylases (HDAC) is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI) as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer.
Methods
We investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival.
Results
Almost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity.
Conclusion
Class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies.