Elevated EZH2 Expression in Invasive Urothelial Carcinoma of the Bladder
H Wang, R Albadine, S Saab, A Magheli, MW Ball, M Gonzalgo, GJ Netto. James Buchanan Brady Urological Institute, Baltimore; Johns Hopkins Medical Institution, Baltimore
Background: The enhancer of Zeste homologue 2 (EZH2) gene functions as a transcriptional repressor via chromatin remodeling and histone methyltransferase activity. EZH2 has been reported to be overexpressed and associated with progression in a variety of solid tumors. We investigated expression of the EZH2 protein in bladder urothelial carcinoma (UrCa) in relation to clinical outcome.
Design: Tissue microarrays (TMA) were constructed from 122 cystectomy specimens obtained from our institutional archives. At least triplicate tissue samples of UrCa and paired benign urothelium were spotted from each cystectomy. A total of 584 TMA spots were evaluated (296 invasive UrCa, 44 non-invasive UrCa, 45 CIS and 199 benign urothelium). IHC analysis was performed using affinity-purified rabbit polyclonal antibodies against human EZH2 (Zymed, CA). Positive nuclear reactivity of EZH2 was scored as the product of percentage and intensity of staining in each spot.
Results: A significantly higher EZH2 expression score was associated with invasive UrCa compared to benign urothelium (mean 1.91 vs 0.33, p< 0.0001). Significantly increased levels of EZH2 expression were observed in invasive vs non-invasive UrCa (mean 1.91 vs 0.96, p = 0.0004). Significantly elevated EZH2 expression was also observed in non-invasive UrCa vs benign urothelium (mean 0.96 vs 0.33, p =0.002). Among 88 matched pairs of invasive UrCa and benign urothelium, expression of EZH2 was again significantly higher in the invasive UrCa (p< 0.00001). Among 20 matched pairs of invasive UrCa and CIS, expression of EZH2 was significantly higher in invasive UrCa (p<0.0001). Although an increased EZH2 expression was observed in UrCa from patients with subsequent recurrence compared to those without recurrence, the difference was not statistically significant (mean score 2.33 vs 1.85, p = 0.27). EZH2 expression did not correlate with pathologic stage (p = 0.65) or presence of lymph node metastasis (p =0.53).
Conclusions: We report significant elevation in EZH2 protein expression in invasive UrCa compared to non-invasive UrCa and benign urothelium. Our findings suggest a potential role of EZH2 in the progression of urothelial carcinoma of the bladder.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 150, Tuesday Afternoon