title: Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  To assess the prognostic value of epidermal growth factor receptor (EGFR) molecular characteristics of head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  HNSCC tumors from patients prospectively enrolled in either an Early Detection Research Network (EDRN) study and treated with surgery without an EGFR-targeted agent (N = 154) or enrolled in a chemoradiation trial involving the EGFR-targeted antibody cetuximab (N = 39) were evaluated for EGFR gene amplification by FISH and EGFR protein by immunohistochemical staining. Fresh-frozen tumors (EDRN) were also evaluated for EGFR protein and site-specific phosphorylation at Y992 and Y1068 using reverse-phase protein array (n = 67). Tumor (n = 50) EGFR and EGFRvIII mRNA levels were quantified using real-time PCR.
  
  
  RESULTS
  EGFR expression by immunohistochemistry (IHC) was significantly higher in the EDRN tumors with EGFR gene amplification (P < 0.001), and a similar trend was noted in the cetuximab-treated cohort. In the EDRN and cetuximab-treated cohorts elevated EGFR by IHC was associated with reduced survival (P = 0.019 and P = 0.06, respectively). Elevated expression of total EGFR and EGFR PY1068 were independently significantly associated with reduced progression-free survival in the EDRN cohort [HR = 2.75; 95% confidence interval (CI) = 1.26-6.00 and HR = 3.29; 95% CI = 1.34-8.14, respectively].
  
  
  CONCLUSIONS
  In two independent HNSCC cohorts treated with or without cetuximab, tumor EGFR levels were indicative of survival. Tumor EGFR PY1068 levels provided prognostic information independent of total EGFR.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wheeler
authors.forename: Doris R
authors.initials: DR
authors.lastname: Siwak
authors.forename: Raymond
authors.initials: R
authors.lastname: Chai
authors.forename: Courtney
authors.initials: C
authors.lastname: LaValle
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cieply
authors.forename: Carol
authors.initials: C
authors.lastname: Sherer
authors.forename: Corwin
authors.initials: C
authors.lastname: Joy
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Athanassios
authors.initials: A
authors.lastname: Argiris
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Egloff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D000068818:Cetuximab; D015331:Cohort Studies; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis; D010766:Phosphorylation; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D066246:ErbB Receptors; D000068818:Cetuximab