Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
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Acknowledgments
We thank Ms. A. Katayama (MD-PhD course student, Gunma University Faculty of Medicine), Dr. T. Hikino, Dr. M.Saito, and Mr. F. Hara (Department of Diagnostic Pathology, Gunma University Graduate School of Medicine) for their excellent technical assistance.
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The authors have no conflict of interest.
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Nakajima, H., Ishikawa, Y., Furuya, M. et al. Protein expression, gene amplification, and mutational analysis of EGFR in triple-negative breast cancer. Breast Cancer 21, 66–74 (2014). https://doi.org/10.1007/s12282-012-0354-1
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DOI: https://doi.org/10.1007/s12282-012-0354-1