High expression of heat shock proteins and heat shock factor-1 distinguishes an aggressive subset of clear cell renal cell carcinoma

Abstract

Aims

Heat shock proteins (HSPs) are a group of molecules induced by a variety of environmental and pathophysiologic stresses, including cancer. HSPs are implicated in the regulation of apoptosis and immunity in neoplasm. Transcription factor heat shock factor1 (HSF1) acts as the master regulator to control HSP expression, and therefore is involved in tumorigenesis. The purpose of this study was to evaluate the expression and clinicopathologic relevance of HSPs and HSF1 in clear cell renal cell carcinoma (ccRCC).

Methods and results

The expression of HSP27, HSP60, HSP70, HSP90 and HSF1 was assessed in 428 cases of ccRCC using immunohistochemistry. High expression of HSP60 and HSP70 was positively correlated with grade and stage. High expression of HSF1 was positively correlated with stage. Univariate and multivariate analyses demonstrated that 216 patients (52%) with tumour expressing 3 or 4 markers in a panel of HSP60, HSP70, HSP90, and HSF1 had a significantly heightened risk for cancer-specific mortality than tumours expressing <3 markers (P<0.0001; concordance index, 0.81).

Conclusions

Immunohistochemical examination of HSPs and HSF1 provides useful prognostic information that may contribute to the design of therapeutic strategies for patients with ccRCC.

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