title: EGFR expression and copy number changes in low T-stage oral squamous cell carcinomas.
abstract: OBJECTIVE
  EGFR-directed therapies are used to treat patients with advanced head and neck squamous cell carcinoma (SCC). As it is still unclear whether or not EGFR amplification represents an early or late event in head and neck SCC progression, we aimed to determine the frequency of abnormalities of EGFR protein and gene copy numbers in early oral SCC.
  
  
  RESULTS
  A tissue microarray of cancer tissue from 120 patients with pT1/2 oral SCC was constructed. We investigated EGFR protein expression by immunohistochemistry. EGFR gene copy enumeration was performed using fluorescence in-situ hybridization (FISH) and the novel automated silver in-situ hybridization (SISH) technology. Of early oral SCC, 19.3% showed high, 57.1% moderate and 23.6% low EGFR expression. EGFR amplification/polysomy was identified in 8% and 9% of cases by FISH and SISH, respectively. EGFR-SISH had a high concordance with EGFR-FISH (kappa value = 1.0), and both methods showed high conformity with EGFR immunohistochemistry (P = 0.001 and P = 0.006, respectively). No correlation was found of EGFR protein expression or gene amplification status with pT or pN stage.
  
  
  CONCLUSIONS
  Only a small subgroup of early oral SCC is characterized by EGFR amplification, which can be identified reliably using EGFR-SISH technology. This finding suggests that EGFR gene amplification mostly occurs in advanced stages of oral SCC.
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. matthias.roessle@usz.ch
authors.forename: Matthias
authors.initials: M
authors.lastname: Rössle
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Weber
authors.forename: Lena
authors.initials: L
authors.lastname: Züllig
authors.forename: Nicole
authors.initials: N
authors.lastname: Graf
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jochum
authors.forename: Sandro J
authors.initials: SJ
authors.lastname: Stöckli
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Gerhard F
authors.initials: GF
authors.lastname: Huber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D018773:Genes, erbB-1; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; fluorescence in-situ hybridization; head and neck squamous cell carcinoma; immunohistochemistry; oral cavity; oropharynx; silver in-situ hybridization