TY - JOUR
T1 - Polycomb group protein EZH2 is frequently expressed in inflammatory breast cancer and is predictive of worse clinical outcome
AU - Gong, Yun
AU - Huo, Lei
AU - Liu, Ping
AU - Sneige, Nour
AU - Sun, Xiaoping
AU - Ueno, Naoto T.
AU - Lucci, Anthony
AU - Buchholz, Thomas A.
AU - Valero, Vicente
AU - Cristofanilli, Massimo
PY - 2011/12/15
Y1 - 2011/12/15
N2 - BACKGROUND: Enhancer of zeste homolog 2 (EZH2), a member of polycomb group proteins, is involved in the regulation of cell cycle progression and has been implicated in various human malignancies, including breast cancer, and also has been associated with aggressive tumor behavior. However, the clinical significance of EZH2 expression in inflammatory breast cancer (IBC), a rare but aggressive type of breast carcinoma, has not been explored. In this retrospective study, the authors examined EZH2 expression in IBC tumors and evaluated the relation between EZH2 expression and patient survival. METHODS: Tissue microarrays of 88 surgically resected IBC tumors were stained immunohistochemically for EZH2, and the authors evaluated the association of EZH2 expression status with clinicopathologic factors and clinical outcome. RESULTS: The median follow-up for the entire cohort was 45.7 months, and the 5-year overall survival (OS) rate was 45%. EZH2 was expressed frequently in IBC tumors (75.7%) and was associated significantly with unfavorable prognostic factors, such as higher tumor grade, negative estrogen receptor status, and triple-negative status (ie, negative for the estrogen, progesterone, and human epidermal growth factor 2 receptors). Univariate survival analysis indicated that patients who had EZH2-positive IBC had a significantly lower 5-year OS rate than patients who had EZH2-negative IBC (P =.01). In multivariate analysis, only positive EZH2 status remained an independent predictor of worse OS. CONCLUSIONS: EZH2 was expressed frequently in IBC tumors. The current results indicated that EZH2 expression status may be used to identify a subset of patients with IBC who have a relatively worse prognosis. Targeting EZH2 also may provide a novel strategy for improving the clinical outcome of patients with IBC.
AB - BACKGROUND: Enhancer of zeste homolog 2 (EZH2), a member of polycomb group proteins, is involved in the regulation of cell cycle progression and has been implicated in various human malignancies, including breast cancer, and also has been associated with aggressive tumor behavior. However, the clinical significance of EZH2 expression in inflammatory breast cancer (IBC), a rare but aggressive type of breast carcinoma, has not been explored. In this retrospective study, the authors examined EZH2 expression in IBC tumors and evaluated the relation between EZH2 expression and patient survival. METHODS: Tissue microarrays of 88 surgically resected IBC tumors were stained immunohistochemically for EZH2, and the authors evaluated the association of EZH2 expression status with clinicopathologic factors and clinical outcome. RESULTS: The median follow-up for the entire cohort was 45.7 months, and the 5-year overall survival (OS) rate was 45%. EZH2 was expressed frequently in IBC tumors (75.7%) and was associated significantly with unfavorable prognostic factors, such as higher tumor grade, negative estrogen receptor status, and triple-negative status (ie, negative for the estrogen, progesterone, and human epidermal growth factor 2 receptors). Univariate survival analysis indicated that patients who had EZH2-positive IBC had a significantly lower 5-year OS rate than patients who had EZH2-negative IBC (P =.01). In multivariate analysis, only positive EZH2 status remained an independent predictor of worse OS. CONCLUSIONS: EZH2 was expressed frequently in IBC tumors. The current results indicated that EZH2 expression status may be used to identify a subset of patients with IBC who have a relatively worse prognosis. Targeting EZH2 also may provide a novel strategy for improving the clinical outcome of patients with IBC.
KW - enhancer of zeste homolog 2
KW - estrogen receptor
KW - human epidermal growth factor receptor 2
KW - inflammatory breast cancer
KW - survival
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U2 - 10.1002/cncr.26179
DO - 10.1002/cncr.26179
M3 - Article
C2 - 21713757
AN - SCOPUS:82555176159
SN - 0008-543X
VL - 117
SP - 5476
EP - 5484
JO - Cancer
JF - Cancer
IS - 24
ER -