Suitability of clear cell renal cell carcinoma to heat shock proteins-inhibitors.

480 Background: Heat shock proteins (HSP) HSP27 and HSP90 are expressed in response to a wide variety of insults, thus allowing the cell to adapt to stress. In cancer cells, both HSP27 and HSP90 may participate to carcinogenesis, suggesting these chaperones as an appealing target for cancer therapeutics. The role of HSP in the development and progression of renal-cell carcinomas (RCCs) remains to be defined. We sought to evaluate a series of clear cell RCCs. Methods: 388 RCCs with clear cell histology available on 10 tissue microarrays were recruited. Each case was represented by 3 neoplastic cores. All these cases were stratified according to the Mayo Clinic SSIGN (Size, Staging, Grading, Necrosis) score into five prognostic groups with increasing worse prognosis (1 to 5). Immunostainings for HSP27 and 90 were performed. A mean score number from the three cores was set per case (percentage x intensity). Results were detailed per number of scorable cases per SSIGN category (1 to 5). Results: 117 and 122 RCCs were respectively available for HSP90 and HSP27 scoring. The remaining samples were lost due to the lack of tissue sections or to the absence of adequate neoplastic cells scorable. HSP90 scored 4,9 in 32 with SSIGN1, 3,5 in 41 SSIGN2, 4,8 in 11 SSIGN3, 4,2 in 22 SSIGN4 and 5 in 3 SSIGN5 patients. HSP27 scored 4,6 in 33 with SSIGN1, 3,1 in 43 SSIGN2, 2,6 in 11 SSIGN3, 3,6 in 24 SSIGN4 and 2,7 in 3 SSIGN5 patients. A significant trend of increasing value for HSP90 has been observed when comparing cases tabled SSIGN1-2 versus SSIGN3-5 (4,2 to 4,6 mean values) (p=0.05); a minor stratification has been observed for HSP27 (3,8 to 3,9) (p=0.08). Conclusions: In conclusion, HSP90 and HSP27 are variable immunoexpressed in a subset of clear cell RCCs, with a trend to higher prognostic SSIGN score. At light of new emerging targeted-therapies in kidney cancer, we report an increasing suitability of these patients to therapies that target the pathways of heat shock protein molecules. Additional learning of the HSP role in clear cell RCCs carcinogenesis is required to guide future therapeutic developments.