title: The association between EGFR variant III, HPV, p16, c-MET, EGFR gene copy number and response to EGFR inhibitors in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  We examine the potential prognostic and predictive roles of EGFR variant III mutation, EGFR gene copy number (GCN), human papillomavirus (HPV) infection, c-MET and p16INK4A protein expression in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
  
  
  METHODS
  We analyzed the archival tumor specimens of 53 patients who were treated in 4 phase II trials for R/M SCCHN. Two trials involved the EGFR inhibitor erlotinib, and 2 trials involved non-EGFR targeted agents. EGFRvIII mutation was determined by quantitative RT-PCR, HPV DNA by Linear Array Genotyping, p16 and c-MET protein expression by immunohistochemistry, and EGFR GCN by FISH.
  
  
  RESULTS
  EGFRvIII mutation, detected in 22 patients (42%), was associated with better disease control, but no difference was seen between erlotinib-treated versus non-erlotinib treated patients. EGFRvIII was not associated with TTP or OS. The presence of HPV DNA (38%), p16 immunostaining (32%), c-MET high expression (58%) and EGFR amplification (27%), were not associated with response, TTP or OS.
  
  
  CONCLUSIONS
  EGFRvIII mutation, present in about 40% of SCCHN, appears to be an unexpected prognostic biomarker associated with better disease control in R/M SCCHN regardless of treatment with erlotinib. Larger prospective studies are required to validate its significance.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Chau
authors.forename: Bayardo
authors.initials: B
authors.lastname: Perez-Ordonez
authors.forename: Katherine
authors.initials: K
authors.lastname: Zhang
authors.forename: Nhu-An
authors.initials: NA
authors.lastname: Pham
authors.forename: James
authors.initials: J
authors.lastname: Ho
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Olga
authors.initials: O
authors.lastname: Ludkovski
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.forename: Eric X
authors.initials: EX
authors.lastname: Chen
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000821:virology; D002294:Carcinoma, Squamous Cell; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000821:virology; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000821:virology; D030361:Papillomavirus Infections / Q000473:pathology* / Q000821:virology; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met