Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer.

Abstract

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.

• Authors: Florian R Fritzsche, Wilko Weichert, Annika Röske, Volker Gekeler, Thomas Beckers, Carsten Stephan, Klaus Jung, Katharina Scholman, Carsten Denkert, Manfred Dietel, Glen Kristiansen
• Journal: BMC cancer (BMC Cancer) Vol. 8 Pg. 381 (Dec 19 2008) ISSN: 1471-2407 [Electronic] England
• PMID: 19099586 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Isoforms
• Repressor Proteins
• HDAC1 protein, human
• Histone Deacetylase 1
• Histone Deacetylase 2
• Histone Deacetylases
• histone deacetylase 3

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Renal Cell (enzymology, metabolism, pathology)
• Chi-Square Distribution
• Cohort Studies
• Gene Expression Regulation, Neoplastic (physiology)
• Histone Deacetylase 1
• Histone Deacetylase 2
• Histone Deacetylases (metabolism)
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Middle Aged
• Protein Isoforms (metabolism)
• Repressor Proteins (metabolism)
• Statistics, Nonparametric
• Tissue Array Analysis