Specifically, they assess the percentage of staining - EZH2 positivity was defined as >20% staining. Clinicopathologic characteristics and oncologic outcomes including recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were compared between patients stratified by EZH2 positivity.
There were 752 patients undergoing RNU that were considered for inclusion – patients were excluded for low-grade disease (188), neoadjuvant chemotherapu (20), MIBC (31) and no staining (131). Of the 376 patients included (median follow-up 36 months) 298 (79.3%) patients were EZH2-negative and 78 (20.7%) were EZH2-positive. While these numbers are small for most diagnoses, for UTUC, this represents a large series.
EZH2 expression was associated with tumor location (ureteric > pelvic), sessile appearance (vs. papillary), presence of necrosis, presence of lymphovascular invasion, and presence of CIS. While EZH2 was a significant predictor for worse RFS (HR 1.63, p=0.033), CSS (HR 2.03, p=0.003), and OS (HR 2.11, p<0.001) on univariate analysis, when accounting for age, pT, pN, and LVI on multivariate analysis, EZH2 remained a significant predictor only for worse OS (HR 1.65, p=0.005); significance was lost for RFS and CSS. However, it should be noted that the multivariable analysis only incorporated some variables that were significant on the univariate analysis – others such as CIS were not included. KM curves were provided.
Based on this, the authors conclude that EZH2 expression appears to be associated with adverse pathologic features and may predict worse oncologic outcomes in patients with high-grade UTUC. However, as with all such retrospective series, association does not imply causation. The role of EZH2 pathways in UTUC pathogenesis remains to be understood.
- It should be noted that the multivariable analysis only incorporated some variables that were significant on the univariate analysis – others such as CIS were not included. Thus, the MV analysis was somewhat flawed.
Co-Authors: Many, senior author: Vitaly Margulis
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC