Department of Diagnostic Pathology, Gunma University, 3-39-22, Maebashi, Gunma, 371-8511, Japan,
Breast Cancer. 2014 Jan;21(1):66-74. doi: 10.1007/s12282-012-0354-1. Epub 2012 Apr 6.
Although triple-negative breast cancer (TNBC) with epidermal growth factor receptor (EGFR) expression has been extensively studied, few studies have simultaneously examined EGFR expression and EGFR gene amplification. Here, we examined the correlations of EGFR expression with EGFR gene amplification, EGFR-activating mutations, and the expression of components of the Akt pathway.
Tumor tissues were obtained from 84 patients with TNBC. We analyzed the expression of EGFR, phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and other relevant proteins using immunohistochemistry. We also analyzed EGFR gene and chromosome 7 copy numbers by dual-color in situ hybridization. DNA was extracted from formalin-fixed paraffin-embedded samples. Analysis of EGFR gene-activating mutations was performed using the smart amplification process version 2 assay.
Most TNBCs expressing EGFR are non-specialized invasive ductal carcinomas, whereas others are likely to be rare specialized carcinomas, such as typical medullary carcinoma, apocrine carcinoma, metaplastic carcinoma, and adenoid cystic carcinoma. EGFR was expressed in samples from 28 of 84 (33.3%) patients, but the EGFR gene was not amplified in any of the 84 samples. There were significant correlations between EGFR expression and the number of polysomic cells and the presence of high polysomy of chromosome 7. However, EGFR expression was not correlated with p-Akt or p-mTOR expression, nor with the other clinicopathological factors recorded in this study. We found no evidence of EGFR gene-activating mutations.
EGFR gene amplification and EGFR-activating mutations might not be the mechanisms leading to the constitutive activation of EGFR in TNBC. Further investigation is needed to clarify the other molecular mechanisms for oncogenic activation of EGFR in TNBC.
尽管已经广泛研究了具有表皮生长因子受体（EGFR）表达的三阴性乳腺癌（TNBC），但很少有研究同时检查 EGFR 表达和 EGFR 基因扩增。在这里，我们研究了 EGFR 表达与 EGFR 基因扩增、EGFR 激活突变以及 Akt 通路成分的表达之间的相关性。
从 84 例 TNBC 患者中获得肿瘤组织。我们使用免疫组织化学法分析 EGFR、磷酸化 Akt（p-Akt）、磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）和其他相关蛋白的表达。我们还通过双色原位杂交分析 EGFR 基因和 7 号染色体拷贝数。从福尔马林固定石蜡包埋样本中提取 DNA。使用智能扩增过程 2 检测法分析 EGFR 基因激活突变。
大多数表达 EGFR 的 TNBC 是非特化性浸润性导管癌，而其他可能是罕见的特化性癌，如典型的髓样癌、大汗腺癌、间变性癌和腺样囊性癌。在 84 例患者的样本中，有 28 例（33.3%）表达 EGFR，但在 84 例样本中均未扩增 EGFR 基因。EGFR 表达与多倍体细胞数量和 7 号染色体高倍体存在之间存在显著相关性。然而，EGFR 表达与 p-Akt 或 p-mTOR 表达以及本研究中记录的其他临床病理因素无关。我们没有发现 EGFR 基因激活突变的证据。
EGFR 基因扩增和 EGFR 激活突变可能不是导致 TNBC 中 EGFR 组成性激活的机制。需要进一步研究以阐明 TNBC 中 EGFR 致癌激活的其他分子机制。
