Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
National Clinical Research Center for Cancer,Tianjin Medical University Cancer Institute and Hospital, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, China.
Virchows Arch. 2020 Aug;477(2):279-289. doi: 10.1007/s00428-020-02773-0. Epub 2020 Feb 21.
Human epidermal growth factor receptor (HER)-2 positive (HER2) breast cancer (BC) has a poor survival rate and is more aggressive in nature. HER2-targeting agents could be beneficial for patients with HER2 BC. In addition, targeted therapy and chemotherapy have been successfully used. However, a few patients are resistant to treatment. ErbB3 binding protein 1 (EBP1) binds to HER3 and inhibits the proliferation and invasive potential of tumor cells. However, its role in HER2 BC has not been demonstrated. In this study, we aimed to analyze the relationship between androgen receptor (AR) and EBP1 expression in HER2 BC. A total of 282 cases (140 cases of HER2 invasive BC and 142 HER2-negative invasive BC) were included in this study. We performed immunohistochemistry (IHC) to analyze the expression of AR and EBP1; thereafter, we evaluated the relationship between these two biomarkers and estrogen receptor (ER), progesterone receptor (PR), HER2, p53, Ki67 expression, and other clinicopathological parameters. Of the HER2 cases, 67 (47.9%) showed high expression of EBP1 (EBP1) and 73 (52.1%) showed low/no expression of EBP1 (EBP1). EBP1 expression was correlated with AR expression, histological grade, and lymphatic metastasis (p < 0.001, < 0.001, and 0.013, respectively). Kaplan-Meier analysis revealed that AR and EBP1 group had poorer overall survival (OS) and disease-free survival (DFS) compared with other groups (AR and EBP1, AR and EBP1, and AR and EBP1). AR and EBP1 expression were independent prognostic factors for OS and DFS in HER2+ BC. This study showed the clinicopathological role of EBP1 and AR in HER2+ BC. Targeting EBP1 may be an effective treatment strategy for patients with AR HER2 BC.
人表皮生长因子受体 2 阳性(HER2)乳腺癌(BC)的存活率低,且具有侵袭性。HER2 靶向药物对 HER2 BC 患者有益。此外,靶向治疗和化疗已成功应用。然而,少数患者对治疗有抵抗性。表皮生长因子受体结合蛋白 1(EBP1)与 HER3 结合,抑制肿瘤细胞的增殖和侵袭潜力。然而,其在 HER2 BC 中的作用尚未得到证实。在这项研究中,我们旨在分析 HER2 BC 中雄激素受体(AR)和 EBP1 表达之间的关系。共纳入 282 例患者(140 例 HER2 浸润性 BC 和 142 例 HER2 阴性浸润性 BC)。我们进行免疫组织化学(IHC)分析以检测 AR 和 EBP1 的表达;此后,我们评估了这两种生物标志物与雌激素受体(ER)、孕激素受体(PR)、HER2、p53、Ki67 表达及其他临床病理参数之间的关系。在 HER2 病例中,67 例(47.9%)EBP1 高表达(EBP1+),73 例(52.1%)EBP1 低/无表达(EBP1-)。EBP1 表达与 AR 表达、组织学分级和淋巴转移相关(p<0.001、<0.001 和 0.013)。Kaplan-Meier 分析显示,与其他组相比,AR 和 EBP1 组的总生存期(OS)和无病生存期(DFS)更差(AR 和 EBP1、AR 和 EBP1+和 AR 和 EBP1-)。AR 和 EBP1 表达是 HER2+BC 患者 OS 和 DFS 的独立预后因素。本研究显示了 EBP1 和 AR 在 HER2+BC 中的临床病理作用。靶向 EBP1 可能是 AR+HER2 BC 患者的有效治疗策略。