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

Hang Wang, Roula Albadine, Ahmed Magheli, Thomas J. Guzzo, Mark W. Ball, Stefan Hinz, Mark P. Schoenberg, George J. Netto, Mark L. Gonzalgo

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)428-433
Number of pages6
JournalUrologic Oncology: Seminars and Original Investigations
Volume30
Issue number4
DOIs
StatePublished - Jul 2012
Externally publishedYes

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Urinary Bladder
Carcinoma
Proteins
Urothelium
Cystectomy
Polycomb-Group Proteins
Proportional Hazards Models
Urinary Bladder Neoplasms
Biomarkers
Immunohistochemistry
Staining and Labeling
Recurrence
Survival
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Urology

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Increased EZH2 protein expression is associated with invasive urothelial carcinoma of the bladder. / Wang, Hang; Albadine, Roula; Magheli, Ahmed; Guzzo, Thomas J.; Ball, Mark W.; Hinz, Stefan; Schoenberg, Mark P.; Netto, George J.; Gonzalgo, Mark L.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 30, No. 4, 07.2012, p. 428-433.

Research output: Contribution to journalArticle

Wang, Hang ; Albadine, Roula ; Magheli, Ahmed ; Guzzo, Thomas J. ; Ball, Mark W. ; Hinz, Stefan ; Schoenberg, Mark P. ; Netto, George J. ; Gonzalgo, Mark L. / Increased EZH2 protein expression is associated with invasive urothelial carcinoma of the bladder. In: Urologic Oncology: Seminars and Original Investigations. 2012 ; Vol. 30, No. 4. pp. 428-433.
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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.",
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AU - Wang, Hang

AU - Albadine, Roula

AU - Magheli, Ahmed

AU - Guzzo, Thomas J.

AU - Ball, Mark W.

AU - Hinz, Stefan

AU - Schoenberg, Mark P.

AU - Netto, George J.

AU - Gonzalgo, Mark L.

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