Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement

C. S. Foster, A. R. Dodson, L. Ambroisine, G. Fisher, H. Møller, J. Clark, G. Attard, J. De-Bono, P. Scardino, V. E. Reuter, C. S. Cooper, D. M. Berney, J. Cuzick

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Abstract

* Background: 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.

* Methods: 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.

* Results: 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 (χ2 trend=31.4, P<0.001), although this distribution did not have prognostic significance.

* Interpretation: 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.

Original languageEnglish
Pages (from-to)1137-1144
Number of pages8
JournalBritish Journal of Cancer
Volume101
Issue number7
DOIs
Publication statusPublished - 25 Aug 2009

Keywords

  • Heat shock protein 27
  • Prognostic biomarker
  • Prostate cancer

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