title: Protein expression, gene amplification, and mutational analysis of EGFR in triple-negative breast cancer.
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.
authors.affiliation: Department of Diagnostic Pathology, Gunma University, 3-39-22, Maebashi, Gunma, 371-8511, Japan, nakajiji0830@gmail.com.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Mio
authors.initials: M
authors.lastname: Furuya
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sano
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohno
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism; D002897:Chromosomes, Human, Pair 7; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology*
chemical_list: C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases