Expression of the polycomb group protein EZH2 and its relation to outcome in patients with urothelial carcinoma of the bladder.
OBJECTIVE
The polycomb group protein Enhancer of Zeste Homolg 2 (EZH2), a repressor of gene transcription, has been linked to the progression of various malignancies. This study was done to examine a potential correlation of EZH2 mRNA expression with clinicopathological parameters and outcome in patients with urothelial carcinoma (UC) of the bladder.


METHODS
We determined the relative EZH2 gene expression by quantitative RT-PCR in tumor specimens from a cohort of 100 patients with UC (mean follow-up 44.2 months). EZH2 expression levels were correlated to pathological tumor features and outcome.


RESULTS
Enhancer of Zeste Homolg 2 was expressed in 90% of the tumor samples. Expression levels increased in parallel with tumor stage (P = 0.002). High grade UC displayed significantly elevated EZH2 levels compared to low grade disease (P < 0.0001). High EZH2 expression was related to an abbreviated time to recurrence in muscle invasive carcinomas (pT >/= 2) (P = 0.028). No such correlation was detected in the group of superficial tumors (pT </= 1) (P = 0.191). High EZH2 expression levels were associated with an increased risk of tumor related death in the univariate analysis (relative risk, 3.1; P = 0.029). This association became non-significant when the prognostic effect of tumor stage was considered in a multivariate model.


CONCLUSIONS
Enhancer of Zeste Homolg 2 expression is related to an aggressive tumor behavior but due to its strong association with pathological features, EZH2 levels do not provide independent prognostic information.
Hinz
Stefan
S
Department of Urology, Universitätsmedizin Berlin, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. stefan.hinz@charite.de
Kempkensteffen
Carsten
C
Christoph
Frank
F
Hoffmann
Michèle
M
Krause
Hans
H
Schrader
Mark
M
Schostak
Martin
M
Miller
Kurt
K
Weikert
Steffen
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
Br J Cancer. 2006 Jan 30;94(2):179-83
16404435
Urology. 2001 May;57(5):852-9
11337281
Cancer Sci. 2006 Jun;97(6):484-91
16734726
Oncogene. 2007 Feb 15;26(7):1028-37
16909110
J Clin Oncol. 2006 Jan 10;24(2):268-73
16330673
J Cell Biochem Suppl. 2001;Suppl 36:129-43
11455578
Cell. 2000 Jan 7;100(1):57-70
10647931
Curr Opin Urol. 2002 May;12(3):239-43
11953681
EMBO J. 2003 Oct 15;22(20):5323-35
14532106
Oncogene. 2004 Feb 26;23(8):1627-30
14716298
Methods Mol Biol. 1998;110:43-61
9918038
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11606-11
14500907
Am J Surg Pathol. 1998 Dec;22(12):1435-48
9850170
Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8570-6
16361539
Nature. 2002 Oct 10;419(6907):624-9
12374981
Neoplasia. 2005 Nov;7(11):1011-9
16331887
Nature. 2006 Feb 16;439(7078):871-4
16357870
Crit Rev Oncol Hematol. 2003 Jun 27;46 Suppl:S67-83
12850529
Urol Int. 2005;75(3):252-7
16215315
Cancer Res. 2006 Apr 15;66(8):4095-9
16618729
Int J Mol Med. 2005 Aug;16(2):349-53
16012774
Int J Cancer. 2006 Oct 1;119(7):1513-8
16557569