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. 2008 Dec 19:8:381.
doi: 10.1186/1471-2407-8-381.

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

Florian R Fritzsche  1 , Wilko Weichert, Annika Röske, Volker Gekeler, Thomas Beckers, Carsten Stephan, Klaus Jung, Katharina Scholman, Carsten Denkert, Manfred Dietel, Glen Kristiansen
Affiliations

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

Florian R Fritzsche et al. BMC 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.

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Figures

Figure 1
Figure 1
HDAC 1 expression in normal and malignant renal tissue. In benign renal tissue HDAC 1 is focally expressed in nuclei of mesangial cells of the glomeruli and also tubular epithelia with a stronger expression in the distal part of the nephron (A). Clear cell RCC negative for HDAC 1, contrasting to the relatively strong staining in adjacent stroma (B). RCC displaying a strong and homogenous nuclear positivity in tumour cells (C). Papillary (D1) and chromophobe (D2) RCC with strong HDAC 1 expression.
Figure 2
Figure 2
HDAC 2 expression in normal and malignant renal tissue. HDAC 2 was found to have a similar expression pattern as HDAC 1 with moderately positive normal glomerular and tubular cells (A). HDAC 2 negative clear cell carcinoma with distinctly positive stromal cells (B). Strong nuclear HDAC 2 expression in clear cell (C), papillary (D1) and chromophobe (D2) histologic subtypes of RCC.
Figure 3
Figure 3
HDAC 3 expression in normal and malignant renal tissue. HDAC 3 expression in normal renal tissue with positive glomerular and tubular epithelial cells (A). Partially sarcomatoid differentiated clear cell RCC with only very few rather weak to moderately positive tumour cells (B). Clear cell (C), papillary (D1) and chromophobe (D2) RCC with strong HDAC 3 expression.
Figure 4
Figure 4
Kaplan-Meier survival curves for renal cell cancer patients according to class I HDAC expression patterns. For none of the HDAC isoforms 1–3 (A-C) a significant prognostic value for the patient survival times could be demonstrated.
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