Polycomb group protein EZH2 is frequently expressed in inflammatory breast cancer and is predictive of worse clinical outcome.

Abstract

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.

• Authors: Yun Gong, Lei Huo, Ping Liu, Nour Sneige, Xiaoping Sun, Naoto T Ueno, Anthony Lucci, Thomas A Buchholz, Vicente Valero, Massimo Cristofanilli
• Journal: Cancer (Cancer) Vol. 117 Issue 24 Pg. 5476-84 (Dec 15 2011) ISSN: 1097-0142 [Electronic] United States
• PMID: 21713757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Cancer Society.

Chemical References

• DNA-Binding Proteins
• Polycomb-Group Proteins
• Repressor Proteins
• Transcription Factors
• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein
• Polycomb Repressive Complex 2

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chemotherapy, Adjuvant
• Cohort Studies
• DNA-Binding Proteins (biosynthesis)
• Enhancer of Zeste Homolog 2 Protein
• Female
• Humans
• Immunohistochemistry
• Inflammatory Breast Neoplasms (drug therapy, metabolism, pathology, surgery)
• Mastectomy
• Microarray Analysis
• Middle Aged
• Neoadjuvant Therapy
• Polycomb Repressive Complex 2
• Polycomb-Group Proteins
• Repressor Proteins (biosynthesis)
• Retrospective Studies
• Transcription Factors (biosynthesis)
• Treatment Outcome
• Young Adult