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.

【摘要 引言】新辅助化疗（Neoadjuvant chemotherapy, NAC）是局部晚期乳腺癌的标准治疗方案。然而，部分肿瘤因其组织学与分子特征，无法对该治疗产生应答。zeste同源增强子2（enhancer of zest homolog 2，简称EZH2）是一种组蛋白甲基转移酶，与低分化乳腺癌及侵袭性肿瘤行为密切相关。

### 研究目的
本研究旨在评估EZH2表达与新辅助化疗应答之间的关联，以及其与人表皮生长因子受体2（HER2）过表达、雌激素受体（ER）、孕激素受体（PR）及Ki-67增殖指数的相关性。

### 研究方法
本研究共纳入60例接受新辅助化疗的局部晚期乳腺癌患者。其中23份石蜡包埋组织块因组织样本量不足，无法完成检测，未纳入分析。对剩余37份标本构建组织微阵列，并开展EZH2免疫组织化学（immunohistochemistry, IHC）分析。根据患者对新辅助化疗的应答情况，将其分为两组。

### 研究结果
EZH2表达与多项不良预后标志物显著相关，包括ER阴性（p = 0.001）、PR阴性（p = 0.042）及高Ki-67增殖指数（p = 0.002）。但高EZH2表达与新辅助化疗应答无显著相关性。

### 研究结论
本研究数据表明，EZH2蛋白表达可能与新辅助化疗的临床应答无关联。后续需开展更大样本量的研究以验证该结论。