Expression of Enhancer of Zeste Homolog 2 (EZH2) in Invasive Neuroendocrine Carcinoma of the Breast
Yun Gong, Jieqing Chen, Jun Wang, Laszlo Radvanyi, Daniel G Rosen, Yun Wu. University of Texas MD Anderson Cancer Center, Houston, TX
Background: Enhancer of Zeste homolog 2 (EZH2), a member of Polycomb Group (PcG) proteins, is involved in the regulation of cell cycle progression and has been implicated in various human malignancies, including beast cancer, and also has been associated with poor clinical outcome of the patients. Invasive neuroendocrine carcinoma (NEC) of the breast is a rare type of tumor that has not been well-studied. Our recent study (Cancer 2010;116:4463–73) indicated that mammary NEC is a distinct type of breast carcinoma associated with aggressive biologic behavior. In this study, we sought to determine the correlation between the expression of EZH2 and clinicopathologic variables as well as survival outcome of the patients with mammary NEC.
Design: Mammary NEC was defined according to 2003 WHO classification of the breast and female genital organs. A total of 64 primary NECs of the breast that were surgically removed between February 1996 and March 2009 were analyzed in this study. Immunhistochemical staining for EZH2 was performed using monoclonal antibody (clone 6A10, dilution 1:200, Novocastra). Nuclear staining in greater than 10% of invasive tumor cells was defined as positive. Patients' information, tumor characteristics and prognostic and predictive biomarkers were retrospectively reviewed. The relationships between EZH2 expression and overall survival (OS), recurrence-free survival (RFS), and other pathologic parameters were examined.
Results: The age of the patients ranged from 34 to 82 years (median: 62 years). The median follow-up was 36 (7-215) months and the 5-year OS and RFS rates were 82.6 (95% confidence interval = 63.0% - 92.4%) and 61.7% (95% confidence interval = 40.7% - 77.2%), respectively. EZH2 expression was found in 26 (40.6%) of the 64 tumors, and was significantly associated with high nuclear grade (p < 0.001), high histologic grade (p < 0.001) and high Ki-67 index (p = 0.0001). However, there as no significant correlation between EZH2 expression and OS (p = 0.183) or RFS (p = 0.101) rates.
Conclusions: Positive EZH2 expression was significantly associated with high nuclear grade, high histologic grade and high Ki67 index. Targeting EZH2 may provide a novel strategy to improve clinical outcome in patients with mammary NEC. Further study with larger series is required to delineate the biologic mechanism of EZH2 in mammary NEC.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 62, Tuesday Afternoon