Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer.
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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ABSTRACT: The heat shock proteins (HSP) constitute a superfamily of chaperone proteins present in all cells and in all cell compartments, operating in a complex interplay with synergistic/overlapping multiplicity of functions, even though the common effect is cell protection. Several reasons explain the need for investigating HSP in prostate cancer: (1) these molecules function as chaperones of tumorigenesis accompanying the emergence of prostate cancer cells, (2) they appear as useful molecular markers associated with disease aggressiveness and with resistance to anticancer therapies including hormone therapy, radiotherapy, chemotherapy and hyperthermia, and (3) they can be used as targets for therapies. The latter can be accomplished by: (i) interrupting the interaction of HSP (mainly HSPC1) with various client proteins that are protected from degradation when chaperoned by the HSP; (ii) using the chaperone and adjuvant capabilities of certain HSP to present antigenic peptides to the immune system, so this system can recognise the prostate tumour cells as foreign to mount an effective antitumoral response; and (iii) using treatment planning models taking into account the HSP expression levels to obtain more effective therapies. In summary, the study of the HSP during tumorigenesis as well as during cancer progression, and the inclusion of treatment designs targeting HSP combined with other treatment modalities, should improve prostate cancer survival in the near future.International Journal of Hyperthermia 01/2010; 26(8):737-47. · 1.92 Impact Factor