Enhancer of Zeste Homologue 2 Expression in Breast Carcinoma Smears in Relationship with p53, Ki-67 and Other Prognostic Parameters

Abstract

Background: The polycomb group protein enhancer of zeste homologue 2 (EZH 2) has been reported as a marker of aggressive breast cancer. The aim of this study was to investigate the correlation between the expression of EZH 2 with p53 and Ki-67 expression and other clinicopathological parameters in primary breast carcinomas in order to determine the role of the above marker as a prognosticator of tumor aggressiveness and patient outcome. Patients and Methods: One hundred primary operable breast cancer patients were investigated in order to identify the expression of EZH 2, Ki-67 and p53 in imprint smears immunocytochemically. The prevalence of expression of these markers was then correlated with clinicopathological parameters. Follow-up was available for all patients. Results: EZH 2 was expressed in 64% of the cases and correlated with higher levels of p53 (relative risk = 3.00, p < 0.0001) and Ki-67 (relative risk = 3.25, p < 0.0001). Malignant cells showed immunoreactivity for all markers in the nucleus. Univariate analysis revealed a strong association between EZH 2 protein expression and tumor grade and size, lymph node metastasis, and HER-2 and estrogen and progesterone receptor status. Multivariable statistical analysis revealed that lymph node metastasis was the main predictor for EZH 2 expression. Decreased patient survival was also significantly associated with EZH 2 expression (p < 0.0001). Conclusions: EZH 2 expression may be a marker of poor prognosis in breast carcinoma patients and has been suggested as a candidate for targeted therapy.

High EZH2 Protein Expression Is Associated with Poor Overall Survival in Patients with Luminal A Breast Cancer

“…We also found a significant correlation between high EZH2 expression and both p53 overexpression and high Ki-67 proliferative index. This is consistent with previous experimental findings that suggest roles for p53 and Ki-67 in regulating EZH2 via its promoter [ 21 22 ].…”

Enhancer of Zeste Homolog 2 as an Independent Prognostic Marker for Cancer: A Meta-Analysis

“…Nineteen studies provided sufficient data for the meta-analysis of the correlation between EZH2 expression and clinicopathological characteristics ( Table 4 ) [ 14 – 17 , 19 , 21 , 23 , 24 , 26 , 31 , 32 , 34 – 37 , 41 – 44 ]. Esophageal carcinoma, renal cell carcinoma, breast cancer gastric cancer, and NSCLC were investigated in detail.…”

Aberrant expression of enhancer of zeste homologue 2, correlated with HIF-1α, refines relapse risk and predicts poor outcome for breast cancer

“…In a subgroup of triple-negative patients, EZH2-positive staining was detected in 85.7% of patients (33). When all breast cancer subtypes were combined, the EZH2 expression rate was 47.4-64.0% (16,17). The corresponding mean mRNA levels of EZH2 in luminal A, luminal B, HER2 + , basal-like and normal-like subtypes were -0.476, 0.145, 0.186, 0.778 and -0.853, respectively (34).…”

“…Indeed, aberrant expression of EZH2 was identified in a variety of solid tumors and might be correlated with the aggressive features of breast cancer such as higher histological grade, increased tumor cell proliferation, lymph node invasion and larger tumor size (4,(9)(10)(11)(12)(13)(14)(15). Although the aggressive effects of EZH2 have been confirmed (4,16,17), the prognostic value of EZH2 in breast cancer remains unclear (9,(16)(17)(18). Kleer et al found that high levels of EZH2 mRNA were correlated with poor distant metastasis-free survival (DMFS) and that overexpression of EZH2 protein predicted inferior overall survival (OS) and disease-free survival (DFS) (9).…”