title: Changes in Epidermal Growth Factor Receptor Gene Copy Number during Oral Carcinogenesis.
abstract: Oral squamous cell carcinoma (OSCC) is a global healthcare problem associated with poor clinical outcomes. Early detection is key to improving patient survival. OSCC may be preceded by clinically recognizable lesions, termed oral potentially malignant disorders (OPMD). As histologic assessment of OPMD does not accurately predict their clinical behavior, biomarkers are required to detect cases at risk of malignant transformation. Epidermal growth factor receptor gene copy number (EGFR GCN) is a validated biomarker in lung non-small cell carcinoma. We examined EGFR GCN in OPMD and OSCC to determine its potential as a biomarker in oral carcinogenesis.
  
  
  
  EGFR GCN was examined by in situ hybridization (ISH) in biopsies from 78 patients with OPMD and 92 patients with early-stage (stages I and II) OSCC. EGFR ISH signals were scored by two pathologists and a category assigned by consensus. The data were correlated with patient demographics and clinical outcomes.
  
  
  
  OPMD with abnormal EGFR GCN were more likely to undergo malignant transformation than diploid cases. EGFR genomic gain was detected in a quarter of early-stage OSCC, but did not correlate with clinical outcomes.
  
  
  
  These data suggest that abnormal EGFR GCN has clinical utility as a biomarker for the detection of OPMD destined to undergo malignant transformation. Prospective studies are required to verify this finding. It remains to be determined if EGFR GCN could be used to select patients for EGFR-targeted therapies.
  
  
  
  Abnormal EGFR GCN is a potential biomarker for identifying OPMD that are at risk of malignant transformation. Cancer Epidemiol Biomarkers Prev; 25(6); 927-35. ©2016 AACR.
authors.affiliation: Centre for Oral Health Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom. Department of Cellular Pathology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom. timothy.bates@ncl.ac.uk.
authors.forename: Timothy
authors.initials: T
authors.lastname: Bates
authors.affiliation: Department of Oral and Maxillofacial Surgery, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Kennedy
authors.affiliation: Oral Diagnosis Department, College of Dentistry, University of Baghdad, Baghdad, Iraq.
authors.forename: Ameena
authors.initials: A
authors.lastname: Diajil
authors.affiliation: Centre for Oral Health Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom. Newcastle University Medicine Malaysia, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Michaela
authors.initials: M
authors.lastname: Goodson
authors.affiliation: Centre for Oral Health Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom. Department of Oral and Maxillofacial Surgery, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomson
authors.affiliation: Department of Cellular Pathology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Doran
authors.affiliation: Department of Cellular Pathology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Heather
authors.initials: H
authors.lastname: Farrimond
authors.affiliation: Oral Pathology, King's College London Dental Institute, London, United Kingdom.
authors.forename: Selvam
authors.initials: S
authors.lastname: Thavaraj
authors.affiliation: Centre for Oral Health Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom. Department of Cellular Pathology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Sloan
authors.affiliation: Centre for Oral Health Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kist
authors.affiliation: Centre for Oral Health Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom. Department of Cellular Pathology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Max
authors.initials: M
authors.lastname: Robinson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D063646:Carcinogenesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D066246:ErbB Receptors