title: Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Pathology, Penn State University School of Medicine and Milton S. Hershey Medical Center, Hershey, PA. Electronic address: jwarrick@hmc.psu.edu.
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Warrick
authors.affiliation: Division of Urology, Department of Surgery, Penn State University School of Medicine and Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.affiliation: Division of Urology, Department of Surgery, Penn State University School of Medicine and Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Kaag
authors.affiliation: Department of Pathology, Penn State University School of Medicine and Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Trey
authors.initials: T
authors.lastname: Bruggeman
authors.affiliation: Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Justin
authors.initials: J
authors.lastname: Cates
authors.affiliation: Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Peter
authors.initials: P
authors.lastname: Clark
authors.affiliation: Department of Pathology, Penn State University School of Medicine and Milton S. Hershey Medical Center, Hershey, PA; Division of Urology, Department of Surgery, Penn State University School of Medicine and Milton S. Hershey Medical Center, Hershey, PA; Department of Biochemistry and Molecular Biology, Penn State University School of Medicine and Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: David J
authors.initials: DJ
authors.lastname: DeGraff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000378:metabolism; D015653:Cystectomy; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism; D055815:Young Adult
chemical_list: C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: Bladder cancer; EZH2; Papillary urothelial carcinoma; Tumor lineage; Urothelial carcinoma in situ; Urothelium