TY - JOUR
T1 - Multi-institutional evaluation of the prognostic significance of EZH2 expression in high-grade upper tract urothelial carcinoma
AU - Singla, Nirmish
AU - Krabbe, Laura Maria
AU - Aydin, Ahmet M.
AU - Panwar, Vandana
AU - Woldu, Solomon L.
AU - Freifeld, Yuval
AU - Wood, Christopher G.
AU - Karam, Jose A.
AU - Weizer, Alon Z.
AU - Raman, Jay D.
AU - Remzi, Mesut
AU - Rioux-Leclercq, Nathalie
AU - Haitel, Andrea
AU - Roscigno, Marco
AU - Bolenz, Christian
AU - Bensalah, Karim
AU - Sagalowsky, Arthur I
AU - Shariat, Shahrokh F.
AU - Lotan, Yair
AU - Bagrodia, Aditya
AU - Kapur, Payal
AU - Margulis, Vitaly
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
KW - Enhancer of zeste homolog 2
KW - Outcomes
KW - Prognostic biomarker
KW - Upper tract urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85046677583&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046677583&partnerID=8YFLogxK
U2 - 10.1016/j.urolonc.2018.04.004
DO - 10.1016/j.urolonc.2018.04.004
M3 - Article
C2 - 29748098
AN - SCOPUS:85046677583
SN - 1078-1439
VL - 36
SP - 343.e1-343.e8
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 7
ER -