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Overexpression of enhancer of zeste homolog 2 (EZH2) characterizes an aggressive subset of prostate cancers and predicts patient prognosis independently from pre- and postoperatively assessed clinicopathological parameters.
Overexpression of enhancer of zeste homolog 2 (EZH2) characterizes an aggressive subset of prostate cancers and predicts patient prognosis independently from pre- and postoperatively assessed clinicopathological parameters.
- Source :
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Carcinogenesis [Carcinogenesis] 2015 Nov; Vol. 36 (11), pp. 1333-40. Date of Electronic Publication: 2015 Sep 21. - Publication Year :
- 2015
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Abstract
- Enhancer of zeste homolog 2 (EZH2) plays an important role in tumor development and progression by interacting with histone and nonhistone proteins. In the current study, we analyzed prevalence and prognostic impact of EZH2 in prostate cancer. EZH2 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12400 prostate cancer specimens. Results were compared to tumor phenotype, biochemical recurrence and molecular subtypes defined by ERG status as well as genomic deletions of 3p, 5q, 6q and PTEN. EZH2 immunostaining was detectable in 56.6% of 10168 interpretable cancers and considered strong in 1.1%, moderate in 12.2% and weak in 43.3% of cases. High EZH2 expression was strongly associated with high Gleason grade (P < 0.0001), advanced pathological tumor stage (P < 0.0001), positive nodal status (P < 0.0001), elevated preoperative PSA level (P = 0.0066), early PSA recurrence (P < 0.0001) and increased cell proliferation P < 0.0001). High-level EZH2 staining was also associated with TMPRSS2:ERG rearrangement and ERG expression in prostate cancers (P < 0.0001) and was linked to deletions of PTEN, 6q15, 5q21 and 3p13 (P < 0.0001 each) particularly in ERG-negative cancers. The prognostic impact of EZH2 was independent of established pre- and postoperatively assessed clinicopathological parameters. EZH2 has strong prognostic impact in prostate cancer and might contribute to the development of a fraction of genetically instable and particularly aggressive prostate cancers. EZH2 analysis might therefore be of clinical value for risk stratification of prostate cancer.<br /> (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Aged
Cell Proliferation
Disease-Free Survival
Enhancer of Zeste Homolog 2 Protein
Gene Expression
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Multivariate Analysis
Neoplasm Recurrence, Local prevention & control
Oncogene Proteins, Fusion genetics
Polycomb Repressive Complex 2 genetics
Postoperative Period
Preoperative Period
Prognosis
Prostate metabolism
Prostate pathology
Prostate surgery
Prostatectomy
Prostatic Neoplasms mortality
Prostatic Neoplasms pathology
Prostatic Neoplasms surgery
Tissue Array Analysis
Neoplasm Recurrence, Local metabolism
Polycomb Repressive Complex 2 metabolism
Prostatic Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 36
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 26392259
- Full Text :
- https://doi.org/10.1093/carcin/bgv137