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Urol Oncol. 2018 Jul;36(7):343.e1-343.e8. doi: 10.1016/j.urolonc.2018.04.004. Epub 2018 May 7.

Multi-institutional evaluation of the prognostic significance of EZH2 expression in high-grade upper tract urothelial carcinoma.

Author information

1
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
2
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, University of Muenster Medical Center, Muenster, Germany.
3
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Hacettepe University, Ankara, Turkey.
4
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
5
Department of Urology, MD Anderson Cancer Center, Houston, TX.
6
Department of Urology, University of Michigan Cancer Center, Ann Arbor, MI.
7
Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA.
8
Department of Urology, Medical University of Vienna, Vienna, Austria.
9
Department of Pathology, Centre Hospitalier Universitaire de Rennes, Rennes, France.
10
Department of Pathology, Medical University Vienna, Vienna, Austria.
11
Department of Urology, Ospedali Riuniti of Bergamo, Bergamo, Italy.
12
Department of Urology, University of Ulm, Ulm, Germany.
13
Department of Urology, Centre Hospitalier Universitaire de Rennes, Rennes, France.
14
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: vitaly.margulis@utsouthwestern.edu.

Abstract

PURPOSE:

Enhancer of zeste homolog 2 is a methyltransferase encoded by the EZH2 gene, whose role in upper tract urothelial carcinoma (UTUC) is poorly understood. We sought to evaluate the prognostic value of EZH2 expression in UTUC.

METHODS:

We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy for high-grade UTUC from 1990 to 2008. Immunohistochemistry for EZH2 was performed on tissue microarrays. Percentage of staining was evaluated, and the discriminative value of EZH2 was tested, with EZH2 positivity defined as>20% staining present. Clinicopathologic characteristics and oncologic outcomes (recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS)) were compared, stratified by EZH2 positivity. The prognostic role of EZH2 was assessed using Kaplan-Meier, univariate (UVA), and multivariate (MVA) Cox regression analyses. Significance was defined for P<0.05.

RESULTS:

A total of 376 patients were included for analysis, with median follow-up 36.0 months. Overall, 78 (20.7%) were EZH2-positive. EZH2 expression was more often associated with ureteral location, lymphovascular invasion, sessile architecture, necrosis, and concomitant carcinoma in situ. On UVA, increased EZH2 expression was a significant predictor for inferior RFS (HR 1.63, P = 0.033), CSS (HR 2.03, P = 0.003), and OS (HR 2.11, P<0.001). On MVA EZH2 remained a significant predictor of worse CSS (HR 1.99 [95% CI: 1.21-3.27], P = 0.007) and OS (HR 1.54 [95% CI: 1.06-2.24], P = 0.024), while significance was lost for RFS.

CONCLUSION:

Increased EZH2 expression is associated with adverse pathologic features and inferior oncologic outcomes in patients with high-grade UTUC. The role of EZH2 biology in UTUC pathogenesis remains to be further elucidated.

KEYWORDS:

Enhancer of zeste homolog 2; Outcomes; Prognostic biomarker; Upper tract urothelial carcinoma

PMID:
29748098
DOI:
10.1016/j.urolonc.2018.04.004
[Indexed for MEDLINE]

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