Journal
BRITISH JOURNAL OF CANCER
Volume 101, Issue 7, Pages 1137-1144Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6605227
Keywords
heat shock protein 27; prostate cancer; prognostic biomarker
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Funding
- Cancer Research UK
- National Cancer Research Institute
- US National Cancer Institute
- Grand Charity of Freemasons
- Rosetrees Trust
- The Bob Champion Cancer Trust
- The Orchid Appeal
- David Koch Foundation
- North Cancer Research Fund
- Medical Research Council [G0501019] Funding Source: researchfish
- National Institute for Health Research [CL-2008-22-001] Funding Source: researchfish
- MRC [G0501019] Funding Source: UKRI
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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 47, 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 (chi(2) 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. British Journal of Cancer (2009) 101, 1137-1144. doi:10.1038/sj.bjc.6605227 www.bjcancer.com Published online 25 August 2009 (C) 2009 Cancer Research UK
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