Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement.
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.
Foster
C S
CS
Division of Cellular Pathology and Molecular Genetics, University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. csfoster@liv.ac.uk
Dodson
A R
AR
Ambroisine
L
L
Fisher
G
G
Møller
H
H
Clark
J
J
Attard
G
G
De-Bono
J
J
Scardino
P
P
Reuter
V E
VE
Cooper
C S
CS
Berney
D M
DM
Cuzick
J
J
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*
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D050783:Proto-Oncogene Proteins c-ets
J Biol Chem. 2007 Jul 27;282(30):21598-608
17510053
Clin Cancer Res. 1995 May;1(5):473-80
9816006
Eur J Biochem. 1995 Jan 15;227(1-2):416-27
7851416
J Urol. 1992 Mar;147(3 Pt 2):798-803
1371552
Prostate Suppl. 2000;9:4-14
11056496
Cancer Res. 1983 Sep;43(9):4297-301
6871865
Mol Cell Biol. 2000 Oct;20(20):7602-12
11003656
Cancer Res. 2000 Dec 15;60(24):7099-105
11156417
Br J Cancer. 2006 Nov 6;95(9):1186-94
17077805
J Biol Chem. 2005 Dec 16;280(50):41439-48
16234246
Int J Hyperthermia. 1996 Jan-Feb;12(1):125-38
8676000
JAMA. 1995 Aug 23-30;274(8):626-31
7637143
Chin Med J (Engl). 2008 Oct 20;121(20):1975-9
19080259
Oncogene. 2007 Apr 19;26(18):2667-73
17043636
In Vivo. 1997 Mar-Apr;11(2):179-84
9179613
Br J Cancer. 2004 Jan 12;90(1):182-8
14710227
Histopathology. 2007 Oct;51(4):452-7
17880526
Mol Cell Biochem. 2009 Jul;327(1-2):1-6
19191007
Cancer Metastasis Rev. 1992 Sep;11(2):197-220
1356648
Biochem Pharmacol. 2008 Jan 15;75(2):383-94
17915194
JAMA. 2005 May 4;293(17):2095-101
15870412
J Cancer Res Clin Oncol. 2009 Feb;135(2):181-9
18758817
Cell Signal. 2009 May;21(5):712-8
19166925
J Natl Cancer Inst. 2000 Oct 4;92(19):1564-72
11018092
J Cell Sci. 1997 Feb;110 ( Pt 3):357-68
9057088
N Engl J Med. 2002 Sep 12;347(11):781-9
12226148
J Pathol. 2002 Jul;197(4):551-65
12115870
Am J Surg Pathol. 2007 Jun;31(6):882-8
17527075
Oncogene. 2008 Mar 27;27(14):1993-2003
17922029
Urology. 1997 Nov;50(5):722-6
9372882
Clin Cancer Res. 2008 Jun 1;14(11):3380-5
18519767
N Engl J Med. 2005 May 12;352(19):1977-84
15888698
Breast Cancer Res Treat. 1995;36(1):93-7
7579511
APMIS. 2008 Oct;116(10):888-95
19132982
Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9616-20
18599451
BJU Int. 2007 Dec;100(6):1240-4
17979924
Cell Stress Chaperones. 2004 Mar;9(1):29-37
15270075
Cell Stress Chaperones. 2009 Sep;14(5):445-57
19224398
Br J Urol. 1993 Jul;72(1):92-7
7511972
CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
15761078
Bioorg Med Chem Lett. 2008 Dec 1;18(23):6142-6
18945615
J Biol Chem. 1992 Jan 15;267(2):794-803
1730670
Biochem Soc Symp. 1999;64:79-89
10207622
CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
18287387
J Cell Biol. 2006 Sep 11;174(6):863-75
16966425
Oncogene. 2004 Aug 5;23(35):5871-9
15184867
Eur Urol. 2008 Feb;53(2):347-54
17544572
Oncol Rep. 2008 Nov;20(5):1165-72
18949417
J Clin Pathol. 1997 Oct;50(10):801-4
9462258
Nature. 2009 Feb 12;457(7231):E1; discussion E2-3
19212347
Mol Pharmacol. 2006 Sep;70(3):869-77
16772519
J Cell Sci. 2004 May 15;117(Pt 12):2569-77
15128872
Prostate. 2000 Sep 15;45(1):58-65
10960843
Cancer Res. 2004 Sep 15;64(18):6595-602
15374973
Biochem Biophys Res Commun. 2004 Jan 30;314(1):143-50
14715258
Cancer Res. 2007 Nov 1;67(21):10455-65
17974989
Hum Pathol. 2009 Jan;40(1):41-9
18755499
Urol Oncol. 2010 Mar-Apr;28(2):145-51
18848789
Neoplasia. 2008 Feb;10(2):177-88
18283340
JAMA. 2004 Jun 9;291(22):2713-9
15187052
Exp Cell Res. 1996 Feb 25;223(1):163-70
8635489
Science. 2005 Oct 28;310(5748):644-8
16254181
Br J Cancer. 2009 Mar 24;100(6):888-93
19293807
Cancer Res. 2005 Dec 1;65(23):11083-93
16322258
Cell. 1994 Sep 23;78(6):1027-37
7923353
Oncogene. 2008 Jan 10;27(3):253-63
17637754
Scand J Urol Nephrol Suppl. 2000;(205):19-43
11144897
J Biol Chem. 2001 Sep 28;276(39):36071-4
11493600
Cancer Res. 2008 Oct 15;68(20):8516-24
18922926
Br J Cancer. 2008 Jul 22;99(2):314-20
18594527
Cell Signal. 2007 Nov;19(11):2379-87
17728103
Neoplasia. 2006 Oct;8(10):826-32
17032499