Co-overexpression of HER2/HER3 is a predictor of impaired survival in breast cancer patients
Co-overexpression of HER2/HER3 is a predictor of impaired survival in breast cancer patients
复制标题
DOI：
10.1016/j.breast.2014.06.011
复制
发表时间：
2014-10-01
期刊：
影响因子：
3.9
通讯作者：
Birner, Peter
中科院分区：
文献类型：
--
作者：
Berghoff, Anna S.;Bartsch, Rupert;Birner, Peter
背景：最近，HER3的表达被认为是转移扩散的独立危险因素。因此，我们研究了HER3表达作为转移性乳腺癌患者预后标记物的作用。方法：从乳腺癌数据库中确定诊断为转移性疾病(内脏和/或脑转移)的不同类型乳腺癌患者。提取各自原发肿瘤的组织样本，进行雌激素受体、孕激素受体、HER2和HER3的免疫组织化学染色。对HER2可疑和HER3阳性病例进行荧光原位杂交(FISH)分析。结果：110例患者的组织标本均可用于分析。21%的肿瘤细胞至少有10%的肿瘤细胞HER3染色强烈、完整、膜性；HER3蛋白表达与HER3基因扩增无关。HER2/HER3共过表达12/110(11%)，HER3过表达与HER2过表达有统计学意义(p=0.02)。未观察到HER3过表达与总生存期、脑转移诊断时间和脑转移发生率之间的相关性。尽管如此，在HER3过度表达的患者中，观察到更高的仅限于大脑的转移行为(p=0.042)。在HER2阳性亚组中，HER3过度表达与确诊为转移性疾病的OS缩短显著相关(中位数17个月比35个月；p=0.04；对数等级检验)。结论：HER2/HER3共同过度表达与HER2阳性转移性乳腺癌患者确诊为转移性疾病的OS受损显著相关。联合抑制HER2和HER3或抑制HER2/HER3异构化可能会改善这一亚组的临床预后。(C)2014爱思唯尔有限公司。保留所有权利。
Background: Recently, HER3-expression was postulated as independent risk factor for metastatic spread. Therefore, we investigated the role of HER3 expression as prognostic marker in metastatic breast cancer patients.Methods: Patients of different breast cancer subtypes diagnosed with metastatic disease (visceral and/or brain metastases) were identified from a breast cancer database. Tissue samples of the respective primary tumors were retrieved, and immunohistochemical staining for estrogen-receptor, progesterone-receptor, HER2, and HER3 was performed. In HER2 equivocal and selected HER3 positive cases, subsequent fluorescent in situ hybridization (FISH) analysis was performed.Results: Tissue specimens of 110 patients were available for this analysis. 21% had strong, complete, membranous HER3 staining of at least 10% of all tumor cells; HER3 protein expression was not associated with HER3 gene amplification. HER2/HER3 co-overexpression was observed in 12/110 (11%) specimens and HER3-overexpression showed a statistically significant association with HER2-overexpression (p = 0.02). No correlation was observed for HER3-overexpression and overall survival (OS), time to diagnosis of brain metastases, and incidence of brain metastases. Still, in patients with HER3 overexpression, a higher rate of 'brain only' metastatic behavior was observed (p = 0.042). In the HER2-positive subgroup, HER3-overexpression was significantly associated with shorter OS from diagnosis of metastatic disease (median 17 vs. 35 months; p = 0.04; log rank test).Conclusions: HER2/HER3 co-overexpression is significantly associated with impaired OS from diagnosis of metastatic disease in patients with HER2-positive metastatic breast cancer. Co-inhibition of HER2 and HER3 or the inhibition of HER2/HER3 hetero-dimerization may improve clinical outcome in this subgroup. (C) 2014 Elsevier Ltd. All rights reserved.