Increased EZH2 protein expression is associated with invasive urothelial carcinoma of the bladder

Abstract Objectives Elevated polycomb group protein Enhancer of Zest Homolog 2 (EZH2) expression has been associated with progression to more advanced disease in a variety of malignancies. We examined EZH2 protein expression levels in bladder tissue specimens from patients with urothelial carcinoma...

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Veröffentlicht in:Urologic oncology 2012-07, Vol.30 (4), p.428-433
Hauptverfasser: Wang, Hang, Ph.D, Albadine, Roula, M.D, Magheli, Ahmed, M.D, Guzzo, Thomas J., M.D., M.P.H, Ball, Mark W., M.D, Hinz, Stefan, M.D, Schoenberg, Mark P., M.D, Netto, George J., M.D, Gonzalgo, Mark L., M.D., Ph.D
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container_end_page 433
container_issue 4
container_start_page 428
container_title Urologic oncology
container_volume 30
creator Wang, Hang, Ph.D
Albadine, Roula, M.D
Magheli, Ahmed, M.D
Guzzo, Thomas J., M.D., M.P.H
Ball, Mark W., M.D
Hinz, Stefan, M.D
Schoenberg, Mark P., M.D
Netto, George J., M.D
Gonzalgo, Mark L., M.D., Ph.D
description Abstract Objectives Elevated polycomb group protein Enhancer of Zest Homolog 2 (EZH2) expression has been associated with progression to more advanced disease in a variety of malignancies. We examined EZH2 protein expression levels in bladder tissue specimens from patients with urothelial carcinoma (UC) and investigated the relationship between EZH2 protein expression and clinical outcomes. Materials and methods Tissue microarrays (TMAs) were constructed using bladder tissue specimens from radical cystectomies performed for UC at our institution between 1994 and 2002. EZH2 expression was measured by immunohistochemistry and scoring was based on percentage and intensity of positive nuclear staining. A receiver operating curve (ROC) was generated to differentiate cancerous from benign lesions using EZH2 protein scores. Recurrence-free survival was estimated using the Kaplan-Meier approach with log-rank test. A multivariate Cox proportional hazards model was used to assess independent contributions. Results A total of 454 TMA specimen spots from 81 patients were evaluated. EZH2 protein levels in invasive high grade UC were significantly elevated compared with adjacent benign urothelium, noninvasive low grade UC, and CIS. EZH2 protein levels were also significantly increased in CIS and noninvasive low grade UC compared with adjacent benign urothelium. We found no association between EZH2 protein expression and clinical outcomes following radical cystectomy in our cohort of patients. Conclusion EZH2 overexpression is a common event in UC of the bladder. Elevated EZH2 protein levels are associated with more aggressive bladder cancer, including invasive UC. EZH2 may therefore serve as a useful biomarker for UC.
doi_str_mv 10.1016/j.urolonc.2010.09.005
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We examined EZH2 protein expression levels in bladder tissue specimens from patients with urothelial carcinoma (UC) and investigated the relationship between EZH2 protein expression and clinical outcomes. Materials and methods Tissue microarrays (TMAs) were constructed using bladder tissue specimens from radical cystectomies performed for UC at our institution between 1994 and 2002. EZH2 expression was measured by immunohistochemistry and scoring was based on percentage and intensity of positive nuclear staining. A receiver operating curve (ROC) was generated to differentiate cancerous from benign lesions using EZH2 protein scores. Recurrence-free survival was estimated using the Kaplan-Meier approach with log-rank test. A multivariate Cox proportional hazards model was used to assess independent contributions. Results A total of 454 TMA specimen spots from 81 patients were evaluated. EZH2 protein levels in invasive high grade UC were significantly elevated compared with adjacent benign urothelium, noninvasive low grade UC, and CIS. EZH2 protein levels were also significantly increased in CIS and noninvasive low grade UC compared with adjacent benign urothelium. We found no association between EZH2 protein expression and clinical outcomes following radical cystectomy in our cohort of patients. Conclusion EZH2 overexpression is a common event in UC of the bladder. Elevated EZH2 protein levels are associated with more aggressive bladder cancer, including invasive UC. EZH2 may therefore serve as a useful biomarker for UC.</description><identifier>ISSN: 1078-1439</identifier><identifier>EISSN: 1873-2496</identifier><identifier>DOI: 10.1016/j.urolonc.2010.09.005</identifier><identifier>PMID: 21396836</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Biomarkers, Tumor - biosynthesis ; Carcinoma, Transitional Cell - metabolism ; Carcinoma, Transitional Cell - pathology ; Carcinoma, Transitional Cell - surgery ; Cystectomy - methods ; Enhancer of Zeste Homolog 2 Protein ; EZH2 ; Female ; Humans ; Immunohistochemistry - statistics &amp; numerical data ; Kaplan-Meier Estimate ; Male ; Medical sciences ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Nephrology. Urinary tract diseases ; Polycomb protein ; Polycomb Repressive Complex 2 - biosynthesis ; Proportional Hazards Models ; Tissue Array Analysis - statistics &amp; numerical data ; Tissue microarray ; Tumors ; Tumors of the urinary system ; Urinary bladder cancer ; Urinary Bladder Neoplasms - metabolism ; Urinary Bladder Neoplasms - pathology ; Urinary Bladder Neoplasms - surgery ; Urinary tract. Prostate gland ; Urology ; Urothelial carcinoma</subject><ispartof>Urologic oncology, 2012-07, Vol.30 (4), p.428-433</ispartof><rights>Elsevier Inc.</rights><rights>2012 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-c10a20d85f24b0135457e9890e400880137b0aa99c289bd2dc03e85609eefd3b3</citedby><cites>FETCH-LOGICAL-c450t-c10a20d85f24b0135457e9890e400880137b0aa99c289bd2dc03e85609eefd3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1078143910002541$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=26181317$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21396836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Hang, Ph.D</creatorcontrib><creatorcontrib>Albadine, Roula, M.D</creatorcontrib><creatorcontrib>Magheli, Ahmed, M.D</creatorcontrib><creatorcontrib>Guzzo, Thomas J., M.D., M.P.H</creatorcontrib><creatorcontrib>Ball, Mark W., M.D</creatorcontrib><creatorcontrib>Hinz, Stefan, M.D</creatorcontrib><creatorcontrib>Schoenberg, Mark P., M.D</creatorcontrib><creatorcontrib>Netto, George J., M.D</creatorcontrib><creatorcontrib>Gonzalgo, Mark L., M.D., Ph.D</creatorcontrib><title>Increased EZH2 protein expression is associated with invasive urothelial carcinoma of the bladder</title><title>Urologic oncology</title><addtitle>Urol Oncol</addtitle><description>Abstract Objectives Elevated polycomb group protein Enhancer of Zest Homolog 2 (EZH2) expression has been associated with progression to more advanced disease in a variety of malignancies. We examined EZH2 protein expression levels in bladder tissue specimens from patients with urothelial carcinoma (UC) and investigated the relationship between EZH2 protein expression and clinical outcomes. Materials and methods Tissue microarrays (TMAs) were constructed using bladder tissue specimens from radical cystectomies performed for UC at our institution between 1994 and 2002. EZH2 expression was measured by immunohistochemistry and scoring was based on percentage and intensity of positive nuclear staining. A receiver operating curve (ROC) was generated to differentiate cancerous from benign lesions using EZH2 protein scores. Recurrence-free survival was estimated using the Kaplan-Meier approach with log-rank test. A multivariate Cox proportional hazards model was used to assess independent contributions. Results A total of 454 TMA specimen spots from 81 patients were evaluated. EZH2 protein levels in invasive high grade UC were significantly elevated compared with adjacent benign urothelium, noninvasive low grade UC, and CIS. EZH2 protein levels were also significantly increased in CIS and noninvasive low grade UC compared with adjacent benign urothelium. We found no association between EZH2 protein expression and clinical outcomes following radical cystectomy in our cohort of patients. Conclusion EZH2 overexpression is a common event in UC of the bladder. Elevated EZH2 protein levels are associated with more aggressive bladder cancer, including invasive UC. EZH2 may therefore serve as a useful biomarker for UC.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - biosynthesis</subject><subject>Carcinoma, Transitional Cell - metabolism</subject><subject>Carcinoma, Transitional Cell - pathology</subject><subject>Carcinoma, Transitional Cell - surgery</subject><subject>Cystectomy - methods</subject><subject>Enhancer of Zeste Homolog 2 Protein</subject><subject>EZH2</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry - statistics &amp; numerical data</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Staging</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Polycomb protein</subject><subject>Polycomb Repressive Complex 2 - biosynthesis</subject><subject>Proportional Hazards Models</subject><subject>Tissue Array Analysis - statistics &amp; numerical data</subject><subject>Tissue microarray</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary bladder cancer</subject><subject>Urinary Bladder Neoplasms - metabolism</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Urinary Bladder Neoplasms - surgery</subject><subject>Urinary tract. 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Urinary tract diseases</topic><topic>Polycomb protein</topic><topic>Polycomb Repressive Complex 2 - biosynthesis</topic><topic>Proportional Hazards Models</topic><topic>Tissue Array Analysis - statistics &amp; numerical data</topic><topic>Tissue microarray</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary bladder cancer</topic><topic>Urinary Bladder Neoplasms - metabolism</topic><topic>Urinary Bladder Neoplasms - pathology</topic><topic>Urinary Bladder Neoplasms - surgery</topic><topic>Urinary tract. Prostate gland</topic><topic>Urology</topic><topic>Urothelial carcinoma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Hang, Ph.D</creatorcontrib><creatorcontrib>Albadine, Roula, M.D</creatorcontrib><creatorcontrib>Magheli, Ahmed, M.D</creatorcontrib><creatorcontrib>Guzzo, Thomas J., M.D., M.P.H</creatorcontrib><creatorcontrib>Ball, Mark W., M.D</creatorcontrib><creatorcontrib>Hinz, Stefan, M.D</creatorcontrib><creatorcontrib>Schoenberg, Mark P., M.D</creatorcontrib><creatorcontrib>Netto, George J., M.D</creatorcontrib><creatorcontrib>Gonzalgo, Mark L., M.D., Ph.D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Urologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Hang, Ph.D</au><au>Albadine, Roula, M.D</au><au>Magheli, Ahmed, M.D</au><au>Guzzo, Thomas J., M.D., M.P.H</au><au>Ball, Mark W., M.D</au><au>Hinz, Stefan, M.D</au><au>Schoenberg, Mark P., M.D</au><au>Netto, George J., M.D</au><au>Gonzalgo, Mark L., M.D., Ph.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased EZH2 protein expression is associated with invasive urothelial carcinoma of the bladder</atitle><jtitle>Urologic oncology</jtitle><addtitle>Urol Oncol</addtitle><date>2012-07-01</date><risdate>2012</risdate><volume>30</volume><issue>4</issue><spage>428</spage><epage>433</epage><pages>428-433</pages><issn>1078-1439</issn><eissn>1873-2496</eissn><abstract>Abstract Objectives Elevated polycomb group protein Enhancer of Zest Homolog 2 (EZH2) expression has been associated with progression to more advanced disease in a variety of malignancies. We examined EZH2 protein expression levels in bladder tissue specimens from patients with urothelial carcinoma (UC) and investigated the relationship between EZH2 protein expression and clinical outcomes. Materials and methods Tissue microarrays (TMAs) were constructed using bladder tissue specimens from radical cystectomies performed for UC at our institution between 1994 and 2002. EZH2 expression was measured by immunohistochemistry and scoring was based on percentage and intensity of positive nuclear staining. A receiver operating curve (ROC) was generated to differentiate cancerous from benign lesions using EZH2 protein scores. Recurrence-free survival was estimated using the Kaplan-Meier approach with log-rank test. A multivariate Cox proportional hazards model was used to assess independent contributions. Results A total of 454 TMA specimen spots from 81 patients were evaluated. EZH2 protein levels in invasive high grade UC were significantly elevated compared with adjacent benign urothelium, noninvasive low grade UC, and CIS. EZH2 protein levels were also significantly increased in CIS and noninvasive low grade UC compared with adjacent benign urothelium. We found no association between EZH2 protein expression and clinical outcomes following radical cystectomy in our cohort of patients. Conclusion EZH2 overexpression is a common event in UC of the bladder. Elevated EZH2 protein levels are associated with more aggressive bladder cancer, including invasive UC. EZH2 may therefore serve as a useful biomarker for UC.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>21396836</pmid><doi>10.1016/j.urolonc.2010.09.005</doi><tpages>6</tpages></addata></record>
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subjects Adult
Aged
Aged, 80 and over
Biological and medical sciences
Biomarkers, Tumor - biosynthesis
Carcinoma, Transitional Cell - metabolism
Carcinoma, Transitional Cell - pathology
Carcinoma, Transitional Cell - surgery
Cystectomy - methods
Enhancer of Zeste Homolog 2 Protein
EZH2
Female
Humans
Immunohistochemistry - statistics & numerical data
Kaplan-Meier Estimate
Male
Medical sciences
Middle Aged
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Staging
Nephrology. Urinary tract diseases
Polycomb protein
Polycomb Repressive Complex 2 - biosynthesis
Proportional Hazards Models
Tissue Array Analysis - statistics & numerical data
Tissue microarray
Tumors
Tumors of the urinary system
Urinary bladder cancer
Urinary Bladder Neoplasms - metabolism
Urinary Bladder Neoplasms - pathology
Urinary Bladder Neoplasms - surgery
Urinary tract. Prostate gland
Urology
Urothelial carcinoma
title Increased EZH2 protein expression is associated with invasive urothelial carcinoma of the bladder
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