Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients
Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients
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DOI：
10.1200/jco.2005.09.055
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发表时间：
2005-02-20
影响因子：
45.3
通讯作者：
Thor, AD
中科院分区：
文献类型：
--
作者：
DiGiovanna, MP;Stern, DF;Thor, AD
目的探讨表皮生长因子受体（EGFR）表达的关系，ErbB-2信号活性在乳腺癌和这种相互作用对患者的预后与早期乳腺cancer.Patients和方法石蜡肿瘤切片收集回顾性从1976年和1983年之间诊断的807例乳腺癌患者。ErbB-2，磷酸化（激活）ErbB-2，和EGFB的免疫组化检测进行，结果与临床病理变量和outcome.Results EGFR的表达检测在15%的807例浸润性乳腺癌，包括35%的306 ErbB-2阳性患者。相反，大多数（87%）EGFIR阳性肿瘤共同过表达ErbB-2。97%的磷酸化ErbB-2肿瘤共同过表达EGFR。ErbB-2磷酸化或ErbB-2和EGFR共同过表达的癌症患者生存期最短。相反，患者的肿瘤是阴性的所有三个标志物和那些肿瘤只表达EGFR或只有nonphosphorylated ErbB-2有一个相对有利的outcome.Conclusion这些数据提供了第一个临床证据，EGFR的表达与激活ErbB-2在人类乳腺癌。我们进一步表明，只有当ErbB-2处于磷酸化（活化）状态或与EGFR共表达时，才观察到ErbB-2过表达的不良预后价值。这些数据表明ErbB-2激活的配体依赖性机制在人类乳腺癌中是重要的。这些结果还表明，靶向EGFR的药物可用于治疗具有活化ErbB-2的肿瘤。(C)2005年，美国临床肿瘤学会。
Purpose To examine the relationship of epidermal growth factor receptor (EGFR) expression to ErbB-2 signaling activity in breast cancer and the impact that this interaction has on the prognosis of patients with early-stage breast cancer.Patients and Methods Paraffin tumor sections were collected retrospectively from 807 breast cancer patients diagnosed between 1976 and 1983. Immunohistochemical assays for ErbB-2, phosphorylated (activated) ErbB-2, and EGFB were performed, and the results were correlated with clinicopathologic variables and outcome.Results EGFR expression was detectable in 15% of 807 invasive breast cancers, including 35% of the 306 ErbB-2-positive patients. Conversely, the majority (87%) of EGFIR-positive tumors co-overexpressed ErbB-2. Ninety-seven percent of tumors with phosphorylated ErbB-2 co-overexpressed EGFR. Patients whose cancers demonstrated ErbB-2 phosphorylation or co-overexpression of ErbB-2 and EGFR had the shortest survival. In contrast, patients whose tumors were negative for all three markers and those tumors that expressed only EGFR or only nonphosphorylated ErbB-2 had a relatively favorable outcome.Conclusion These data provide the first clinical evidence that EGFR expression is linked to activation of ErbB-2 in human breast cancers. We have further shown that the adverse prognostic value of ErbB-2 overexpression is observed only when ErbB-2 is in the phosphorylated (activated) state or coexpressed with EGFR. These data suggest that ligand-dependent mechanisms of ErbB-2 activation are important in human breast cancer. These results also suggest that agents targeting EGFR may be useful in the treatment of tumors with activated ErbB-2. (C) 2005 by American Society of Clinical Oncology.