Expression of heat shock protein 70 in renal cell carcinoma and its relation to tumor progression and prognosis
U. Ramp1, C. Mahotka1, S. Heikaus1, T. Shibata1, M.O. Grimm2, R. Willers3 and H.E. Gabbert1
1Institute of Pathology, 2Department of Urology and 3Computer Center, Heinrich-Heine University Hospital, Duesseldorf, Germany
Offprint requests to: Uwe Ramp, MD, Institute of Pathology, Heinrich-Heine University Hospital, Moorenstr. 5, D-40225 Duesseldorf, Germany. e-mail: Ramp@med.uni-duesseldorf.de
Summary. Heat shock proteins (HSPs) play an important role in the cellular response to environmental stress and exert a cytoprotective effect. Especially HSP70 is an effective inhibitor of apoptosis, suggesting a role of HSP70 in carcinogenesis and tumor progression. To explore the relevance of HSP70 in renal cell carcinomas (RCCs), we analyzed nuclear and cytoplasmic HSP70 protein expression in formalin-fixed tissue from 145 clear cell RCCs by immuno-histochemistry as well as Western blot analysis.
Nuclear HSP70 expression was found in all RCCs and 75% of the tumors also exhibited a cytoplasmic HSP70 staining. Importantly, RCCs showed significantly reduced cytoplasmic (p=0.001) and combined nuclear/cytoplasmic (p=0.0022) HSP70 expression when compared with their cells of origin. A significant (p=0.0176) decrease of nuclear HSP70 expression became evident from well to poorly differentiated clear cell RCCs. Quite similarly, a trend (p=0.0558) for reduced combined nuclear/cytoplasmic HSP70 expression was shown from early (pT1) to advanced (pT3) tumor stages. Nevertheless, no correlation between HSP70 expression and patients´ survival became evident.
In conclusion, our investigation demonstrates a significant decrease of antiapoptotic HSP70 protein expression during carcinogenesis and during progression from well (G1) to poorly (G3) differentiated clear cell RCCs. Our results suggest that HSP70-mediated inhibition of apoptosis seems to be of minor importance for carcinogenesis and tumor progression in RCCs. Histol Histopathol 22, 1099-1107 (2007)
Key words: HSP70-expression, Renal cell carcinoma, Apoptosis, Carcinogenesis, Tumor progression