Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer

• Published in: Urologic oncology Vol. 34; no. 6; pp. 258.e1 - 258.e6
• Main Authors: Warrick, Joshua I., M.D, Raman, Jay D., M.D, Kaag, Matthew, M.D, Bruggeman, Trey, B.S, Cates, Justin, M.D, Clark, Peter, M.D, DeGraff, David J., Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2016
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Bladder cancer; Carcinoma in Situ - diagnosis; Carcinoma in Situ - metabolism; Cystectomy; Enhancer of Zeste Homolog 2 Protein - metabolism; EZH2; Female; Humans; Immunohistochemistry; Male; Middle Aged; Papillary urothelial carcinoma; Tissue Array Analysis; Tumor lineage; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - metabolism; Urology; Urothelial carcinoma in situ; Urothelium; Urothelium - metabolism; Young Adult; Urothelial carcinoma in situ; Tumor lineage; Papillary urothelial carcinoma; Bladder cancer; EZH2; Urothelium
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2016.02.011

Abstract Background Studies evaluating enhancer of zeste homolog 2 (EZH2) expression and oncologic outcomes in bladder cancer have been discrepant. EZH2 expression in noninvasive bladder cancer is not well studied. We thus set out to address the discrepancy in previous reports, and to study expression of EZH2 in noninvasive bladder cancer and its associations, in a large cystectomy cohort. Materials and methods EZH2 expression was evaluated in tissue microarray material (invasive and noninvasive cancer). Associations between EZH2 expression and oncologic outcomes, tumor stage, and disease type were determined. Receiver operating characteristic analysis was performed for EZH2 expression in the diagnosis of invasive carcinoma and flat carcinoma in situ (CIS) compared to benign urothelium. Results EZH2 expression was most common in CIS, followed by invasive carcinoma, noninvasive papillary urothelial carcinoma, and benign urothelium, in decreasing order ( P <0.05 all comparisons, linear model). The receiver operating characteristic analysis demonstrated an area under the curve of 0.92 for CIS and 0.83 for invasive carcinoma, both compared to benign urothelium. At a cutoff of≥4, this corresponded to sensitivities of 89% and 73%, and specificities of 82% and 82%, for CIS and invasive carcinoma, respectively. The EZH2 expression was not associated with oncologic outcomes, including recurrence-free survival and death from bladder cancer. The EZH2 expression status (positive or negative) of noninvasive and invasive carcinomas taken from the same bladder correlated ( P = 0.05, Fisher exact). Conclusion That EZH2 status of noninvasive and invasive cancer correlated in individual patients suggests that EZH2 may be a marker of lineage. EZH2 may offer diagnostic utility, particularly in flat urothelial CIS vs. benign urothelium. The present study supports that EZH2 expression in bladder cancer is not predictive of oncologic outcome.