TY - JOUR
T1 - Clinical and biological relevance of enhancer of zeste homolog 2 in triple-negative breast cancer
AU - Hussein, Yaser R.
AU - Sood, Anil K.
AU - Bandyopadhyay, Sudeshna
AU - Albashiti, Bassam
AU - Semaan, Assaad
AU - Nahleh, Zeina
AU - Roh, Juwon
AU - Han, Hee Dong
AU - Lopez-Berestein, Gabriel
AU - Ali-Fehmi, Rouba
N1 - Funding Information:
Part of this research was supported by grants from the National Institutes of Health, Bethesda, MD, ( CA128797 , RC2GM092599 , U54 CA151668 ), Department of Defense, Washington DC, ( BC085265 ), and the Laura and John Arnold Foundation, Houston, TX .
PY - 2012/10
Y1 - 2012/10
N2 - The polycomb group protein, enhancer of zeste homolog 2, is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer. We examined the clinical and biological significance of enhancer of zeste homolog 2 expression in triple-negative breast cancers. Tissue microarrays were constructed with invasive breast cancer cases and stained with the enhancer of zeste homolog 2, cytokeratin 5/6, epidermal growth factor receptor 1, and p53. The expression of these markers was correlated with clinicopathologic variables and patients' outcome. Furthermore, in vivo enhancer of zeste homolog 2 gene silencing was achieved using small interfering RNA incorporated into chitosan nanoparticles. Of 261 cases of invasive breast cancer, high expression of the enhancer of zeste homolog 2 was detected in 87 (33%) cases, and it was strongly associated with a triple-negative breast cancer phenotype (P <.001) compared with all other non-triple-negative breast cancers. Furthermore, high enhancer of zeste homolog 2 was significantly associated with high histologic grade (P =.01), estrogen receptor negativity (P <.001), progesterone receptor negativity (P <.001), epidermal growth factor receptor positivity (P =.04), and high p53 expression (P <.001). Survival analysis demonstrated that patients with high enhancer of zeste homolog 2 had a poorer overall survival compared with those with low enhancer of zeste homolog 2 (P =.03), and it retained its significance as an independent prognostic factor (P =.02). In addition, enhancer of zeste homolog 2 gene silencing resulted in a significant reduction in tumor growth (P <.01) in the orthotopic MB-231 mouse model of breast carcinoma. Our results show that high enhancer of zeste homolog 2 expression is significantly associated with triple-negative breast cancer and decreased survival. Enhancer of zeste homolog 2 may represent a potential therapeutic target for this aggressive disease, which warrants further investigation.
AB - The polycomb group protein, enhancer of zeste homolog 2, is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer. We examined the clinical and biological significance of enhancer of zeste homolog 2 expression in triple-negative breast cancers. Tissue microarrays were constructed with invasive breast cancer cases and stained with the enhancer of zeste homolog 2, cytokeratin 5/6, epidermal growth factor receptor 1, and p53. The expression of these markers was correlated with clinicopathologic variables and patients' outcome. Furthermore, in vivo enhancer of zeste homolog 2 gene silencing was achieved using small interfering RNA incorporated into chitosan nanoparticles. Of 261 cases of invasive breast cancer, high expression of the enhancer of zeste homolog 2 was detected in 87 (33%) cases, and it was strongly associated with a triple-negative breast cancer phenotype (P <.001) compared with all other non-triple-negative breast cancers. Furthermore, high enhancer of zeste homolog 2 was significantly associated with high histologic grade (P =.01), estrogen receptor negativity (P <.001), progesterone receptor negativity (P <.001), epidermal growth factor receptor positivity (P =.04), and high p53 expression (P <.001). Survival analysis demonstrated that patients with high enhancer of zeste homolog 2 had a poorer overall survival compared with those with low enhancer of zeste homolog 2 (P =.03), and it retained its significance as an independent prognostic factor (P =.02). In addition, enhancer of zeste homolog 2 gene silencing resulted in a significant reduction in tumor growth (P <.01) in the orthotopic MB-231 mouse model of breast carcinoma. Our results show that high enhancer of zeste homolog 2 expression is significantly associated with triple-negative breast cancer and decreased survival. Enhancer of zeste homolog 2 may represent a potential therapeutic target for this aggressive disease, which warrants further investigation.
KW - Breast cancer
KW - EZH2
KW - Triple-negative
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U2 - 10.1016/j.humpath.2011.12.004
DO - 10.1016/j.humpath.2011.12.004
M3 - Article
C2 - 22436627
AN - SCOPUS:84866516020
SN - 0046-8177
VL - 43
SP - 1638
EP - 1644
JO - Human Pathology
JF - Human Pathology
IS - 10
ER -