title: Rare occurrence of EGFRvIII deletion in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor and is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) cases. The EGFR truncation mutation, EGFR variant III (EGFRvIII), harbors an in-frame deletion of exons 2-7 (801 bp) that leads to the constitutive activation of downstream signaling. EGFRvIII has been reported in ∼40% of glioblastomas (GBM), but its presence in HNSCC remains controversial.
  
  
  METHODS
  EGFRvIII deletion in 638 HNSCC samples was analyzed using: (i) quantitative Real-Time polymerase chain reaction (qRT-PCR) on 108 HNSCC samples with direct detection of the EGFRvIII breakpoint, (ii) RNA-Seq analysis on 7 HNSCC tumor tissues and 425 The Cancer Genome Atlas (TCGA) HNSCC samples, and (iii) immunohistochemistry (IHC) for EGFRvIII using an established antibody (L8A4) on a tissue microarray of 105 HNSCC samples.
  
  
  RESULTS
  qRT-PCR did not show the presence of EGFRvIII in any of the samples analyzed. Furthermore, we could not detect any EGFRvIII transcripts in the RNA-Seq data of the seven HNSCC samples. However, 2 samples out of 425 TCGA HNSCC samples had EGFRvIII specific reads. EGFRvIII IHC results were assessed as negative for all samples.
  
  
  CONCLUSIONS
  Our results firmly establish that EGFRvIII is very rare in HNSCC as only 2 out of 638 (0.31%) samples we analyzed overall, or 2 out of 540 (0.37%) using mRNA based approaches, were positive for EGFRvIII. EGFRvIII is extremely rare in HNSCC and the clinical significance remains unclear. We propose not to include EGFRvIII testing in regular diagnostic tests for HNSCC.
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Khattri
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA; Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brägelmann
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
authors.forename: Michaela K
authors.initials: MK
authors.lastname: Keck
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Dinali
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Brown
authors.affiliation: Vanderbilt University, Nashville, TN, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stricker
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
authors.forename: Anish
authors.initials: A
authors.lastname: Munagala
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Research Center, Chicago, IL, USA.
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Research Center, Chicago, IL, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lingen
authors.affiliation: Institute for Genomics and Systems Biology, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Research Center, Chicago, IL, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: White
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Research Center, Chicago, IL, USA.
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA; Institute for Genomics and Systems Biology, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Research Center, Chicago, IL, USA. Electronic address: tseiwert@medicine.bsd.uchicago.edu.
authors.forename: Tanguy Y
authors.initials: TY
authors.lastname: Seiwert
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D017931:DNA Primers; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017423:Sequence Analysis, RNA
chemical_list: D017931:DNA Primers; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; Epidermal growth factor variant III; Head and neck squamous cell carcinoma