title: Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma.
abstract: BACKGROUND
  Clinical trials of agents targeting epidermal growth factor receptor (EGFR) in esophageal carcinoma (EC) have indicated a minority subgroup responsive to anti-EGFR therapies. Other investigations suggest increases in EGFR copy number are associated with poor prognosis in EC, but have used a variety of different techniques and tested numbers remain small. A validated assay for EGFR copy number in EC is needed, to allow investigation of EGFR copy number gain as a predictive biomarker for the anti-EGFR responsive subgroup of patients. We developed a scoring system in EC based upon established systems for EGFR fluorescence in-situ hybridisation (FISH) in lung cancer, and applied this in a series of 160 UK patients with advanced EC.
  
  
  RESULTS
  Dual colour FISH on formalin fixed paraffin embedded (FFPE) biopsies were scored independently by two operators as: disomy (score = 1), low trisomy (score = 2), high trisomy (score = 3), low polysomy (score = 4), high polysomy (score = 5) and amplification (score = 6). EGFR FISH positive cases (scores 5 and 6) were found in 32/160 (20 %) tumours, with high polysomy in 22 (13.8 %) and amplification in 10 (6.3 %). Two independent operator scores for FISH positivity were 100 % concordant. EGFR FISH positive status was not associated with clinic-pathological features. EGFR amplification was associated with worse survival (HR = 2.64, 95 % CI 1.04 to 6.71, p = 0.03).
  
  
  CONCLUSIONS
  Our FISH scoring system for EGFR in advanced EC identifies a significant subgroup (20.0 %) of FISH positive patients. EGFR amplification, which is found in 6.3 %, is associated with poor survival. It is not known if there is a role for EGFR targeted treatment in this subgroup of patients, however we are now utilising this EGFR FISH assay and scoring system in biopsies from clinical trials utilising anti-EGFR targeted therapies.
authors.affiliation: Division of Applied Medicine, University of Aberdeen, Aberdeen, AB25 2ZD UK.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Dahle-Smith
authors.affiliation: Department of Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZD UK.
authors.forename: David
authors.initials: D
authors.lastname: Stevenson
authors.affiliation: Department of Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZD UK.
authors.forename: Doreen
authors.initials: D
authors.lastname: Massie
authors.affiliation: Division of Applied Medicine, University of Aberdeen, Aberdeen, AB25 2ZD UK.|Department of Pathology, University of Aberdeen, Aberdeen, AB25 2ZD UK.
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Murray
authors.affiliation: Centre for Statistics in Medicine (CSM), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD UK.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Dutton
authors.affiliation: Centre for Statistics in Medicine (CSM), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD UK.
authors.forename: Corran
authors.initials: C
authors.lastname: Roberts
authors.affiliation: Eli Lilly and Company, 440 Route 22 East, Bridgewater, NJ 08807 USA.
authors.forename: David
authors.initials: D
authors.lastname: Ferry
authors.affiliation: Department of Medical Genetics, University of Aberdeen, Aberdeen, AB25 2ZD UK.
authors.forename: Aileen
authors.initials: A
authors.lastname: Osborne
authors.affiliation: Department of Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZD UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Clark
authors.affiliation: Division of Applied Medicine, University of Aberdeen, Aberdeen, AB25 2ZD UK.
authors.forename: Russell D
authors.initials: RD
authors.lastname: Petty
authors.affiliation: Division of Applied Medicine, University of Aberdeen, Aberdeen, AB25 2ZD UK.|Department of Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZD UK.
authors.forename: Zosia
authors.initials: Z
authors.lastname: Miedzybrodzka
keywords: EGFR Copy Number; Esophageal Carcinoma; Esophago-gastric junctional carcinoma