Article

Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer

Department of Oncology, Karolinska Institutet, Stockholm, Sweden.
Apmis (Impact Factor: 1.92). 10/2008; 116(10):888-95. DOI: 10.1111/j.1600-0463.2008.01051.x
Source: PubMed

ABSTRACT Heat shock proteins (HSPs) protect cells against stress-associated injury and are overexpressed in several malignant tumors. We aimed to investigate their value as prognostic markers in prostate cancer. A tissue microarray (TMA) was constructed of 289 prostate cancers from radical prostatectomy (RP) specimens with median follow-up of 48.9 months. Slides were immunostained for HSP27, HSP60 and HSP70. Intensity and extent of immunoreactivity (IR) and their product (IRp) was evaluated by two observers. The IRp of HSP27 and HSP60, but not of HSP70, significantly predicted biochemical recurrence (p=0.014, 0.034 and 0.160, respectively). Recurrence-free survival in patients with strong HSP27 and HSP60 staining was shorter than in those with weak expression (p=0.019 and 0.001, respectively). IRp of HSP27 and HSP60 correlated with Gleason score (p<0.01). HSP60 was an independent predictor of biochemical recurrence in multivariate analysis, including extraprostatic extension, margin status, seminal vesicle invasion and Gleason score. Weighted kappa for interobserver agreement of HSP27, HSP60 and HSP70 IR was 0.613-0.823 for intensity and 0.584-0.719 for IRp, but only 0.036-0.244 for extent, raising the question whether staining extent should be estimated on TMA. We conclude that HSP27 and HSP60 are predictors of biochemical recurrence after RP.

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    • "Biopsy Prostate 107 patients WB; IHC HSP60 is overexpressed in tumors and strongly associated with prognostic clinical parameters (Castilla et al., 2010) Tissue Cervical 20 patients; 20 controls 2-DE; RT-PCR; WB Increased HSP60 expression (Hwang et al., 2009) Tissue Prostate 289 patients IHC; TMA HSP60 overexpression was correlated with both biochemical recurrence and Gleason score (Glaessgen et al., 2008) Tissue Bladder 42 patients; 10 controls IHC HSP60 low expression levels correlated with higher tumor stage. Loss of HSP60 expression was correlated with tumor infiltration (Lebret et al., 2003) Tissue Breast 149 patients IHC; TMA No association was found between HSP60 and prognosis (Sebastiani et al., 2006 "
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    • "HSPs play important roles in folding, intracellular localization, and degradation of cellular proteins, but the cellular role of HSPs in cancers is not completely understood. However, some reports suggest that particularly high HSP 27, 32, 70 and 90 expression levels are associated with a poor prognosis and drug resistance for certain cancers, including carcinomas of the stomach, liver, and prostate, and also osteosarcomas (Kondo et al., 2007; Glaessgen et al., 2008; Banerji, 2009). Inhibition of these proteins is associated with good response in cancer cells. "
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    • ", DM Berney 6 and J Cuzick 2 on behalf of the Trans-Atlantic Prostate Group expression in a large cohort of well-characterised and conservatively managed patients (Cuzick et al, 2006) with respect to the prediction of tumour aggression. Our original observation that Hsp-27 predicts clinical recurrence in prostate cancer was supported by the finding from a subsequent study that the protein level increases after androgen ablation and is cytoprotective in hormone-refractory prostate cancer (Rocchi et al, 2004), and, more recently, by two studies on men undergoing radical prostatectomy (Glaessgen et al, 2008; Miyake et al, 2008). "
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