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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    ABSTRACT: First discovered in 1962, heat shock proteins (HSPs) are highly studied with about 35,500 publications on the subject to date. HSPs are highly conserved, function as molecular chaperones for a large panel of "client" proteins and have strong cytoprotective properties. Induced by many different stress signals, they promote cell survival in adverse conditions. Therefore, their roles have been investigated in several conditions and pathologies where HSPs accumulate, such as in cancer. Among the diverse mammalian HSPs, some members share several features that may qualify them as cancer biomarkers. This review focuses mainly on three inducible HSPs: HSP27, HPS70, and HSP90. Our survey of recent literature highlights some recurring weaknesses in studies of the HSPs, but also identifies findings that indicate that some HSPs have potential as cancer biomarkers for successful clinical applications.
    Frontiers in Oncology 11/2011; 1:37. DOI:10.3389/fonc.2011.00037
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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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    ABSTRACT: Possible synergistic cytotoxic and apoptotic effects of gossypol with zoledronic acid on DU-145 cells were explored, along with the rationale behind any observed synergism due to the different apoptotic proteins involved. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 activity were measured to verify apoptosis. Human Apoptosis Array was used to evaluate apoptotic proteins. The synergistic cytotoxic combination treatment had a versatile effect on apoptotic proteins, through inhibition of anti-apoptotic proteins (including cIAP-1, cIAP-2, survivin, livin, claspin, p53, p21, PON-2 and heat shock proteins) and concurrently the induction of pro-apoptotic proteins (Bad, Bax, Fas, FADD, cleaved caspase-3 and p27). Both drugs had a minimal toxicity profile comparing to cytotoxic agents. Combination treatments targeting many pivotal apoptosis-related proteins may be a rationale option for treatment of prostate cancer.
    Cell Biology International 09/2009; 33(11):1165-72. DOI:10.1016/j.cellbi.2009.08.006 · 1.64 Impact Factor
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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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    ABSTRACT: This study was performed to test the hypothesis that expression of small heat shock protein Hsp-27 is, at diagnosis, a reliable predictive biomarker of clinically aggressive prostate cancer. A panel of tissue microarrays constructed from a well-characterised cohort of 553 men with conservatively managed prostate cancer was stained immunohistochemically to detect Hsp-27 protein. Hsp-27 expression was compared with a series of pathological and clinical parameters, including outcome. Hsp-27 staining was indicative of higher Gleason score (P<0.001). In tissue cores having a Gleason score >7, the presence of Hsp-27 retained its power to independently predict poor clinical outcome (P<0.002). Higher levels of Hsp-27 staining were almost entirely restricted to cancers lacking ERG rearrangements (chi2 trend=31.4, P<0.001), although this distribution did not have prognostic significance. This study has confirmed that, in prostate cancers managed conservatively over a period of more than 15 years, expression of Hsp-27 is an accurate and independent predictive biomarker of aggressive disease with poor clinical outcome (P<0.001). These findings suggest that apoptotic and cell-migration pathways modulated by Hsp-27 may contain targets susceptible to the development of biologically appropriate chemotherapeutic agents that are likely to prove effective in treating aggressive prostate cancers.
    British Journal of Cancer 09/2009; 101(7):1137-44. DOI:10.1038/sj.bjc.6605227 · 4.82 Impact Factor
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