Positive Expression of Enhancer of Zeste Homolog 2 (EZH2) Predicts Shorter Overall Survival in Patients with Inflammatory Breast Cancer
Y Gong, L Huo, N Sneige, M Cristofanilli. The University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Enhancer of Zeste homolog 2 (EZH2), a member of Polycomb Group (PcG) proteins, is a known repressor of gene transcription and has been reported to be implicated in stem cell regulation and cancer development and progression. We sought to determine the relationship between the expression of this candidate stem cell marker and the prognosis of patients with inflammatory breast cancer (IBC), a rare but the most lethal form of breast carcinoma.
Design: Tissue microarray samples from 85 surgically removed IBCs between September 1994 and August 2004 were analyzed. Patients' information, tumor characteristics and prognostic and predictive biomarkers were retrospectively reviewed. Immunhistochemical staining for EZH2 was performed using monoclonal antibody (clone 6A10, dilution 1:200, Novocastra). Nuclear staining in greater than10% of tumor cells was defined as positive. The relationships between overall survival (OS) and EZH2 expression, other pathologic parameters, and biomarkers were examined.
Results: The age of the patients ranged from 23 to 75 years (median: 49.5 years). Median follow-up time was 8.43 years. Fifty-two deaths occurred by the time of analysis. Median OS was 4.04 years (95% CI, 2.85, 10.2). EZH2 expression was found in 53 (64%) of the 83 IBCs, ER expression in 35 (42%), PR expression in 29 (35%), and HER2 overexpression and/or amplification in 32 (39%). Univariate analysis of OS calculated by the Kaplan-Meier method revealed that poorer OS was significantly associated with positive EZH2 expression (p=0.01) and negative ER status (p=0.006). The 5-year OS for patients with tumors expressing EZH2 was 32.1%, compared to 64.2% without EZH2 expression (log rank P = 0.01). There was no significant correlation between OS and histologic type, nuclear grade, lymphovascular invasion, nodal status, PR status, or HER2 status. In addition, EZH2 expression was more frequently seen in tumors with higher nuclear grade (p=0.03) and negative ER status (p<0.01).
Conclusions: IBC patients with positive EZH2 expression and negative ER status had a significantly poorer prognosis. Positive EZH2 expression was significantly associated with higher nuclear grade and negative ER status. These findings indicate that EZH2 may serve as a novel biomarker for predicting prognosis and may be a potential candidate for targeted therapy in patients with IBC.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 22, Wednesday Afternoon