Enhancer of Zeste Homolog 2 (EZH2) Expression Is Associated with Metastasis and Adverse Clinical Outcome in Clear Cell Renal Cell Carcinoma
Bin Xu, Samuel Abourbih, Kanishka Sircar, Wassim Kassouf, Armen Aprikian, Simon Tanguay, Fadi Brimo. McGill University Health Center, Montreal, QC, Canada; University of Texas MD Anderson Cancer Center, Houston, TX
Background: Enhancer of Zester Homolog 2 (EZH2), a histone methyltransferase mediating chromatin condensation and epigenetic modulation has been shown to be over-expressed in various human carcinomas and to be associated with adverse clinico-pathological characteristics and biologic behavior. The expression of EZH2 in renal cell carcinoma (RCC) is poorly characterized with conflicting results from a limited number of studies.
Design: Using tissue microarrays, EZH2 immnoexpression was evaluated in 223 clear cell (CRCC) and 21 papillary (PRCC) carcinoma cases, both in the primary and metastatic settings (45% and 55% of cases, respectively).
Results: EZH-2 expression was present in 75% and 76% of all CRCCs and PRCCs, respectively. In comparison with primary CRCCs in which 67% (61/91) of cases stained for EZH2, metastatic CRCCs expressed the marker more commonly (81% or 107/132) (c2 test, p < 0.05). Furthermore, in comparison to primary tumors, metastatic tumors significantly over-expressed the marker in terms of staining intensity, percentage of positivity per core, and H-score (one way ANOVA, p < 0.000001).
These observations were confirmed in a cohort of 22 matched primary and metastatic cases. In primary tumors, EZH2 expression was associated with higher nuclear grade. Among the 22 locally advanced primary tumors (pT3/4) and 43 metastatic RCCs in which clinical follow-up was available, patients who suffered RCC-related deaths significantly over-expressed the marker in comparison to those who did not.Figure 1. Overexpression of EZH2 in metastasis (C and D), while the primary clear cell RCC of the same patient shows no expression of EZH2 (A and B).
Conclusions: EZH2 expression is associated with metastasis and worse clinical outcome in RCC. Our study, together with emerging evidence derived from other human carcinomas, indicate that EZH2 is a key molecule driving oncogenesis, tumor invasiveness, and metastasis.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 85, Tuesday Morning