title: Exon 8 amplification of epidermal growth factor receptor (EGFR) in invasive breast carcinomas.
abstract: OBJECTIVE
  The rate of EGFR amplification in breast cancer ranges between 0% and 15%. Recent studies have focused on the amplification status of cytosine-adenine (CA) repeats in intron 1 of the gene and correlated it with increased EGFR protein. The aim of this study was to investigate, for the first time, the significance of coding exon 8 amplification of EGFR in invasive breast cancer.
  
  
  RESULTS
  We investigated, by means of real-time polymerase chain reaction (PCR), the amplification status of exon 8 of the EGFR gene in 148 paraffin-embedded tissue sections, 115 with invasive breast carcinoma and 33 controls. Immunohistochemistry was utilized to detect EGFR and human epidermal growth factor receptor 2 (HER2) expression. Univariate and multivariate statistical analyses were performed for the evaluation of our results. EGFR amplification was observed in 7.8% of the patients, and EGFR was immunodetected in 9.6%. EGFR amplification was correlated positively with EGFR expression (P < 0.0001), HER2 expression (P = 0.023), coexpression of EGFR/HER2 (P < 0.0001) and nuclear grade (P = 0.047), and inversely with ER protein expression (P = .047).
  
  
  CONCLUSIONS
  It appears that amplification of the coding sequence exon 8 exhibits similar biological behaviour to amplification of the regulatory sequence in intron 1, leading to elevated levels of EGFR protein.
authors.affiliation: 1st Department of Pathology, Medical SchoolDepartment of Clinical Therapeutic, Alexandra General Hospital, University of Athens, Athens, Greece.
authors.forename: Efthimia
authors.initials: E
authors.lastname: Souka
authors.forename: Evaggelos
authors.initials: E
authors.lastname: Alexiadis
authors.forename: Irini
authors.initials: I
authors.lastname: Theohari
authors.forename: Ioanna
authors.initials: I
authors.lastname: Giannopoulou
authors.forename: Christos
authors.initials: C
authors.lastname: Papadimitriou
authors.forename: Lydia
authors.initials: L
authors.lastname: Nakopoulou
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D005784:Gene Amplification; D018773:Genes, erbB-1; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors