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Dahle-Smith Å, Stevenson D, Massie D, et al. Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma. Mol Cytogenet. 2015;8:78doi: 10.1186/s13039-015-0181-0.
Dahle-Smith, �. �., Stevenson, D., Massie, D., Murray, G. I., Dutton, S. J., Roberts, C., Ferry, D., Osborne, A., Clark, C., Petty, R. D., & Miedzybrodzka, Z. (2015). Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma. Molecular cytogenetics, 878. https://doi.org/10.1186/s13039-015-0181-0
Dahle-Smith, Åsa, et al. "Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma." Molecular cytogenetics vol. 8 (2015): 78. doi: https://doi.org/10.1186/s13039-015-0181-0
Dahle-Smith Å, Stevenson D, Massie D, Murray GI, Dutton SJ, Roberts C, Ferry D, Osborne A, Clark C, Petty RD, Miedzybrodzka Z. Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma. Mol Cytogenet. 2015 Oct 17;8:78. doi: 10.1186/s13039-015-0181-0. eCollection 2015. PMID: 26478746; PMCID: PMC4609119.
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Mol Cytogenet. 2015 Oct 17;8:78. doi: 10.1186/s13039-015-0181-0. eCollection 2015.

Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma.

Molecular cytogenetics

Åsa Dahle-Smith, David Stevenson, Doreen Massie, Graeme I Murray, Susan J Dutton, Corran Roberts, David Ferry, Aileen Osborne, Caroline Clark, Russell D Petty, Zosia Miedzybrodzka

Affiliations

  1. Division of Applied Medicine, University of Aberdeen, Aberdeen, AB25 2ZD UK.
  2. Department of Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZD UK.
  3. Department of Pathology, University of Aberdeen, Aberdeen, AB25 2ZD UK.
  4. 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.
  5. Eli Lilly and Company, 440 Route 22 East, Bridgewater, NJ 08807 USA.
  6. Department of Medical Genetics, University of Aberdeen, Aberdeen, AB25 2ZD UK.

PMID: 26478746 PMCID: PMC4609119 DOI: 10.1186/s13039-015-0181-0

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).

CONCLUSION: 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.

Keywords: EGFR Copy Number; Esophageal Carcinoma; Esophago-gastric junctional carcinoma

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