title: Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement.
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 (chi2 trend=31.4, P<0.001), although this distribution did not have prognostic significance.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cellular Pathology and Molecular Genetics, University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. csfoster@liv.ac.uk
authors.forename: C S
authors.initials: CS
authors.lastname: Foster
authors.forename: A R
authors.initials: AR
authors.lastname: Dodson
authors.forename: L
authors.initials: L
authors.lastname: Ambroisine
authors.forename: G
authors.initials: G
authors.lastname: Fisher
authors.forename: H
authors.initials: H
authors.lastname: Møller
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.forename: G
authors.initials: G
authors.lastname: Attard
authors.forename: J
authors.initials: J
authors.lastname: De-Bono
authors.forename: P
authors.initials: P
authors.lastname: Scardino
authors.forename: V E
authors.initials: VE
authors.lastname: Reuter
authors.forename: C S
authors.initials: CS
authors.lastname: Cooper
authors.forename: D M
authors.initials: DM
authors.lastname: Berney
authors.forename: J
authors.initials: J
authors.lastname: Cuzick
mesh_terms: D000368:Aged; D015321:Gene Rearrangement; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis* / Q000502:physiology; D006360:Heat-Shock Proteins; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D050783:Proto-Oncogene Proteins c-ets
references.citation: J Biol Chem. 2007 Jul 27;282(30):21598-608
references.pmid: 17510053
references.citation: Clin Cancer Res. 1995 May;1(5):473-80
references.pmid: 9816006
references.citation: Eur J Biochem. 1995 Jan 15;227(1-2):416-27
references.pmid: 7851416
references.citation: J Urol. 1992 Mar;147(3 Pt 2):798-803
references.pmid: 1371552
references.citation: Prostate Suppl. 2000;9:4-14
references.pmid: 11056496
references.citation: Cancer Res. 1983 Sep;43(9):4297-301
references.pmid: 6871865
references.citation: Mol Cell Biol. 2000 Oct;20(20):7602-12
references.pmid: 11003656
references.citation: Cancer Res. 2000 Dec 15;60(24):7099-105
references.pmid: 11156417
references.citation: Br J Cancer. 2006 Nov 6;95(9):1186-94
references.pmid: 17077805
references.citation: J Biol Chem. 2005 Dec 16;280(50):41439-48
references.pmid: 16234246
references.citation: Int J Hyperthermia. 1996 Jan-Feb;12(1):125-38
references.pmid: 8676000
references.citation: JAMA. 1995 Aug 23-30;274(8):626-31
references.pmid: 7637143
references.citation: Chin Med J (Engl). 2008 Oct 20;121(20):1975-9
references.pmid: 19080259
references.citation: Oncogene. 2007 Apr 19;26(18):2667-73
references.pmid: 17043636
references.citation: In Vivo. 1997 Mar-Apr;11(2):179-84
references.pmid: 9179613
references.citation: Br J Cancer. 2004 Jan 12;90(1):182-8
references.pmid: 14710227
references.citation: Histopathology. 2007 Oct;51(4):452-7
references.pmid: 17880526
references.citation: Mol Cell Biochem. 2009 Jul;327(1-2):1-6
references.pmid: 19191007
references.citation: Cancer Metastasis Rev. 1992 Sep;11(2):197-220
references.pmid: 1356648
references.citation: Biochem Pharmacol. 2008 Jan 15;75(2):383-94
references.pmid: 17915194
references.citation: JAMA. 2005 May 4;293(17):2095-101
references.pmid: 15870412
references.citation: J Cancer Res Clin Oncol. 2009 Feb;135(2):181-9
references.pmid: 18758817
references.citation: Cell Signal. 2009 May;21(5):712-8
references.pmid: 19166925
references.citation: J Natl Cancer Inst. 2000 Oct 4;92(19):1564-72
references.pmid: 11018092
references.citation: J Cell Sci. 1997 Feb;110 ( Pt 3):357-68
references.pmid: 9057088
references.citation: N Engl J Med. 2002 Sep 12;347(11):781-9
references.pmid: 12226148
references.citation: J Pathol. 2002 Jul;197(4):551-65
references.pmid: 12115870
references.citation: Am J Surg Pathol. 2007 Jun;31(6):882-8
references.pmid: 17527075
references.citation: Oncogene. 2008 Mar 27;27(14):1993-2003
references.pmid: 17922029
references.citation: Urology. 1997 Nov;50(5):722-6
references.pmid: 9372882
references.citation: Clin Cancer Res. 2008 Jun 1;14(11):3380-5
references.pmid: 18519767
references.citation: N Engl J Med. 2005 May 12;352(19):1977-84
references.pmid: 15888698
references.citation: Breast Cancer Res Treat. 1995;36(1):93-7
references.pmid: 7579511
references.citation: APMIS. 2008 Oct;116(10):888-95
references.pmid: 19132982
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9616-20
references.pmid: 18599451
references.citation: BJU Int. 2007 Dec;100(6):1240-4
references.pmid: 17979924
references.citation: Cell Stress Chaperones. 2004 Mar;9(1):29-37
references.pmid: 15270075
references.citation: Cell Stress Chaperones. 2009 Sep;14(5):445-57
references.pmid: 19224398
references.citation: Br J Urol. 1993 Jul;72(1):92-7
references.pmid: 7511972
references.citation: CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
references.pmid: 15761078
references.citation: Bioorg Med Chem Lett. 2008 Dec 1;18(23):6142-6
references.pmid: 18945615
references.citation: J Biol Chem. 1992 Jan 15;267(2):794-803
references.pmid: 1730670
references.citation: Biochem Soc Symp. 1999;64:79-89
references.pmid: 10207622
references.citation: CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
references.pmid: 18287387
references.citation: J Cell Biol. 2006 Sep 11;174(6):863-75
references.pmid: 16966425
references.citation: Oncogene. 2004 Aug 5;23(35):5871-9
references.pmid: 15184867
references.citation: Eur Urol. 2008 Feb;53(2):347-54
references.pmid: 17544572
references.citation: Oncol Rep. 2008 Nov;20(5):1165-72
references.pmid: 18949417
references.citation: J Clin Pathol. 1997 Oct;50(10):801-4
references.pmid: 9462258
references.citation: Nature. 2009 Feb 12;457(7231):E1; discussion E2-3
references.pmid: 19212347
references.citation: Mol Pharmacol. 2006 Sep;70(3):869-77
references.pmid: 16772519
references.citation: J Cell Sci. 2004 May 15;117(Pt 12):2569-77
references.pmid: 15128872
references.citation: Prostate. 2000 Sep 15;45(1):58-65
references.pmid: 10960843
references.citation: Cancer Res. 2004 Sep 15;64(18):6595-602
references.pmid: 15374973
references.citation: Biochem Biophys Res Commun. 2004 Jan 30;314(1):143-50
references.pmid: 14715258
references.citation: Cancer Res. 2007 Nov 1;67(21):10455-65
references.pmid: 17974989
references.citation: Hum Pathol. 2009 Jan;40(1):41-9
references.pmid: 18755499
references.citation: Urol Oncol. 2010 Mar-Apr;28(2):145-51
references.pmid: 18848789
references.citation: Neoplasia. 2008 Feb;10(2):177-88
references.pmid: 18283340
references.citation: JAMA. 2004 Jun 9;291(22):2713-9
references.pmid: 15187052
references.citation: Exp Cell Res. 1996 Feb 25;223(1):163-70
references.pmid: 8635489
references.citation: Science. 2005 Oct 28;310(5748):644-8
references.pmid: 16254181
references.citation: Br J Cancer. 2009 Mar 24;100(6):888-93
references.pmid: 19293807
references.citation: Cancer Res. 2005 Dec 1;65(23):11083-93
references.pmid: 16322258
references.citation: Cell. 1994 Sep 23;78(6):1027-37
references.pmid: 7923353
references.citation: Oncogene. 2008 Jan 10;27(3):253-63
references.pmid: 17637754
references.citation: Scand J Urol Nephrol Suppl. 2000;(205):19-43
references.pmid: 11144897
references.citation: J Biol Chem. 2001 Sep 28;276(39):36071-4
references.pmid: 11493600
references.citation: Cancer Res. 2008 Oct 15;68(20):8516-24
references.pmid: 18922926
references.citation: Br J Cancer. 2008 Jul 22;99(2):314-20
references.pmid: 18594527
references.citation: Cell Signal. 2007 Nov;19(11):2379-87
references.pmid: 17728103
references.citation: Neoplasia. 2006 Oct;8(10):826-32
references.pmid: 17032499