EZH2 Protein Expression and Tumor Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Abstract

Introduction Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer. However, some tumors will not respond to this treatment due to histological and molecular features. The protein EZH2 (enhancer of zest homolog 2) is a histone methyltransferase that is correlated with poorly differentiated breast carcinomas and aggressive tumor behavior. Purpose The present study evaluated the association between EZH2 expression and response to NAC, and its correlation with HER2 overexpression, estrogen and progesterone receptors (ER, PR) and Ki-67 proliferation index. Methods A total of 60 patients with locally advanced breast cancer treated with NAC were selected for this study. Twenty-three paraffin blocks had not enough material for tissue resection, and were not evaluated. A tissue microarray based in immunohistochemistry (IHC) analysis of EZH2 was performed for the remaining 37 specimens. Patients were divided into two groups based on response to NAC. Results EZH2 expression was significantly associated with markers of poor prognosis such as ER negativity (p = 0.001), PR negativity (p = 0.042) and high Ki-67 proliferation index (p = 0.002). High EZH2 expression was not correlated with the response to NAC. Conclusions Our data suggested that EZH2 protein expression may not correlate with the clinical response to NAC. Other studies with more patients are needed to confirm this observation.

Expression of EZH2 in endometrial carcinoma and its effects on proliferation and invasion of endometrial carcinoma cells

“…A total of 1443 cases of breast cancer tissues were immunohistochemically stained by a concurrent study, and the results showed that high expression of EZH2 was closely related to tumor size and pathological type. Long-term follow-up observation showed that high expression of EZH2 had important clinical value in the prognosis of distant tumor metastasis ( 19 ). All these studies indicated that EZH2 was highly expressed in different malignancies, and no significant correlation was observed between its expression and the age or gender of patients.…”

Wedelolactone Targets EZH2-mediated Histone H3K27 Methylation in Mantle Cell Lymphoma

“…It has been shown that EZH2 is frequently overexpressed in many cancer types including lymphomas, breast, prostate, lung, brain, and liver cancer, and moreover, it is critical for cancer cell proliferation (6)(7)(8)(9)(10). Few reports have proposed mechanisms by which the PRC2 complex controlled methylation level.…”

EZH2 Protein Expression in Triple-negative Breast Cancer Treated With Neoadjuvant Chemotherapy: An Exploratory Study of Association With Tumor Response and Prognosis

“…Only one other study examined this question, and although their findings were similar, they included only 11 TNBC patients and only examined tumor samples from a tissue microarray. 31 In our study we evaluated whole tissue sections of core biopsies in 63 TNBC patients, providing a larger and more definitive investigation of this question. Research by Yomitoubian and colleagues demonstrated that EZH2 inhibition in TNBC human breast cancer cell lines in mouse models does not affect primary tumor growth but impairs distant metastasis.…”

“…Hence accordingly, EZH2 over expression might be linked to resistance to NAC and/or relapse following NAC. To date, only one study, which included only 11 TNBC cases, examined the association between EZH2 over expression and resistance to NAC, and this study did not address the issue of relapse after NAC 31. In our study we used immunohistochemistry to determine if EZH2 protein overexpression is associated with response to NAC, and whether it is associated with the development of metastatic disease in patients with TNBC who have received NAC.…”