title: Nuclear epidermal growth factor receptor and p16 expression in head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) and p16 (a surrogate marker of human papillomavirus [HPV] infection) expression are strong prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  We examined expression levels of total and nuclear EGFR as well as p16 status based on evidence that nuclear EGFR may have a role in DNA damage repair.
  
  
  METHODS
  An HPV-negative (SQ20B) and an HPV-positive (UMSCC47) HNSCC cell line were examined for EGFR and γH2AX expression. A tissue microarray containing 123 cores obtained from 101 HNSCC tumors was analyzed for EGFR expression by automated quantitative analysis and p16 expression by immunohistochemical staining, and these results were correlated with available clinical data.
  
  
  RESULTS
  SQ20B had higher EGFR expression than UMSCC47. Nuclear localization of EGFR on activation with transforming growth factor-α was observed in SQ20B, but not in UMSCC47. SQ20B also had increased γH2AX foci compared to UMSCC47, suggesting that SQ20B has more DNA damage compared to UMSCC47. Total and nuclear EGFR was reliably obtained from 80 of 101 patients. p16 levels were determined in 87 of 101 patients. p16 levels were strongly associated with the oropharyngeal subsite and poorly differentiated histology. Expression of total and nuclear EGFR was higher in p16-negative tumors compared to p16-positive tumors (Wilcoxon rank test, P = .038 and P = .014, respectively).
  
  
  CONCLUSIONS
  Further studies are required to determine a mechanistic link between these two prognostic factors and the significance of EGFR localization to nucleus in DNA damage repair pathway activation.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Hatim
authors.initials: H
authors.lastname: Husain
authors.forename: Amanda
authors.initials: A
authors.lastname: Psyrri
authors.forename: Ana
authors.initials: A
authors.lastname: Markovic
authors.forename: Theodore
authors.initials: T
authors.lastname: Rampias
authors.forename: Eirini
authors.initials: E
authors.lastname: Pectasides
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Robbert
authors.initials: R
authors.lastname: Slebos
authors.forename: Wendell G
authors.initials: WG
authors.lastname: Yarbrough
authors.forename: Barbara
authors.initials: B
authors.lastname: Burtness
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck; D046888:Tissue Array Analysis
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D066246:ErbB Receptors