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

Åsa Dahle-Smith (Lead / Corresponding author), David Stevenson, Doreen Massie, Graeme I. Murray, Susan J. Dutton, Corran Roberts, David Ferry, Aileen Osborne, Caroline Clark, Russell D. Petty, Zosia Miedzybrodzka

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    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.

    Original languageEnglish
    Article number78
    Number of pages9
    JournalMolecular Cytogenetics
    Volume8
    DOIs
    Publication statusPublished - 17 Oct 2015

    Fingerprint

    Aberrations
    Epidermal Growth Factor
    Carcinoma
    Fluorescence In Situ Hybridization
    Fluorescence
    Amplification
    Biopsy
    Trisomy
    Assays
    Clinical Trials
    Survival
    Biomarkers
    Epidermal Growth Factor Receptor
    Paraffin
    Formaldehyde
    Tumors
    Lung Neoplasms
    Therapeutics
    Color

    Cite this

    Dahle-Smith, Å., Stevenson, D., Massie, D., Murray, G. I., Dutton, S. J., Roberts, C., ... Miedzybrodzka, Z. (2015). Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma. Molecular Cytogenetics, 8, [78]. https://doi.org/10.1186/s13039-015-0181-0
    Dahle-Smith, Åsa ; Stevenson, David ; Massie, Doreen ; Murray, Graeme I. ; Dutton, Susan J. ; Roberts, Corran ; Ferry, David ; Osborne, Aileen ; Clark, Caroline ; Petty, Russell D. ; Miedzybrodzka, Zosia. / Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma. In: Molecular Cytogenetics. 2015 ; Vol. 8.
    @article{36ed9217869e479490f5f3120d9dff3f,
    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).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.",
    author = "{\AA}sa Dahle-Smith and David Stevenson and Doreen Massie and Murray, {Graeme I.} and Dutton, {Susan J.} and Corran Roberts and David Ferry and Aileen Osborne and Caroline Clark and Petty, {Russell D.} and Zosia Miedzybrodzka",
    year = "2015",
    month = "10",
    day = "17",
    doi = "10.1186/s13039-015-0181-0",
    language = "English",
    volume = "8",
    journal = "Molecular Cytogenetics",
    issn = "1755-8166",
    publisher = "Springer Verlag",

    }

    Dahle-Smith, Å, Stevenson, D, Massie, D, Murray, GI, Dutton, SJ, Roberts, C, Ferry, D, Osborne, A, Clark, C, Petty, RD & Miedzybrodzka, Z 2015, 'Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma', Molecular Cytogenetics, vol. 8, 78. https://doi.org/10.1186/s13039-015-0181-0

    Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma. / Dahle-Smith, Åsa (Lead / Corresponding author); Stevenson, David; Massie, Doreen; Murray, Graeme I.; Dutton, Susan J.; Roberts, Corran; Ferry, David; Osborne, Aileen; Clark, Caroline; Petty, Russell D.; Miedzybrodzka, Zosia.

    In: Molecular Cytogenetics, Vol. 8, 78, 17.10.2015.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma

    AU - Dahle-Smith, Åsa

    AU - Stevenson, David

    AU - Massie, Doreen

    AU - Murray, Graeme I.

    AU - Dutton, Susan J.

    AU - Roberts, Corran

    AU - Ferry, David

    AU - Osborne, Aileen

    AU - Clark, Caroline

    AU - Petty, Russell D.

    AU - Miedzybrodzka, Zosia

    PY - 2015/10/17

    Y1 - 2015/10/17

    N2 - 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.

    AB - 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.

    U2 - 10.1186/s13039-015-0181-0

    DO - 10.1186/s13039-015-0181-0

    M3 - Article

    VL - 8

    JO - Molecular Cytogenetics

    JF - Molecular Cytogenetics

    SN - 1755-8166

    M1 - 78

    ER -