title: Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas.
abstract: OBJECTIVE
  High epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC.
  
  
  METHODS
  EGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points.
  
  
  RESULTS
  Forty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P < .05 and P < .01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors.
  
  
  CONCLUSIONS
  High EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232-6307, USA. Christine.Chung@Vanderbilt.edu
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
authors.forename: Kim
authors.initials: K
authors.lastname: Ely
authors.forename: Loris
authors.initials: L
authors.lastname: McGavran
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: Joel
authors.initials: J
authors.lastname: Parker
authors.forename: Natalie
authors.initials: N
authors.lastname: Parker
authors.forename: Carolyn
authors.initials: C
authors.lastname: Jarrett
authors.forename: Jesse
authors.initials: J
authors.lastname: Carter
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Murphy
authors.forename: James
authors.initials: J
authors.lastname: Netterville
authors.forename: Brian B
authors.initials: BB
authors.lastname: Burkey
authors.forename: Robert
authors.initials: R
authors.lastname: Sinard
authors.forename: Anthony
authors.initials: A
authors.lastname: Cmelak
authors.forename: Shawn
authors.initials: S
authors.lastname: Levy
authors.forename: Wendell G
authors.initials: WG
authors.lastname: Yarbrough
authors.forename: Robbert J C
authors.initials: RJ
authors.lastname: Slebos
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
mesh_terms: D000782:Aneuploidy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016019:Survival Analysis
chemical_list: D066246:ErbB Receptors