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Esophageal carcinoma cell line with high EGFR polysomy is responsive to gefitinib

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Abstract

Purpose

It has previously been shown that gefitinib-treated patients with epidermal growth factor receptor (EGFR) gene amplification or high polysomy had a statistically significant improvement in response, time to progression, and survival in non-small cell lung cancer (NSCLC). Only few studies utilizing anti-EGFR treatment in advanced esophageal adenocarcinomas have been performed and the results have been heterogeneous. The aim of this study was to evaluate EGFR-targeted therapy with gefitinib in esophageal adenocarcinoma with a high EGFR polysomy.

Methods

Novel esophageal cell lines PT6216 and LN6216c were established from primary tumor and lymph node metastasis of a patient with highly aggressive and metastatic adenocarcinoma. Pathological examination including tumor differentiation and prognostic marker analysis, immunohistochemical EGFR expression analysis, EGFR fluorescence in situ hybridization, and mutation analysis were performed. Response of novel cell lines to gefitinib treatment was evaluated by cell proliferation and vitality assays. Fifty-four esophageal adenocarcinoma specimens were evaluated for EGFR gene copy gain.

Results

The primary tumor cell line PT6216 and the lymph node cell line LN6216c show a homogenously high polysomy for EGFR determined by FISH analysis. Cell proliferation and vitality are highly sensitive to the tyrosine kinase inhibitor gefitinib compared to esophageal control cells without a high polysomy for EGFR. High polysomy for EGFR was found in 35 % of patients.

Conclusion

We show for the first time a significant treatment response to the EGFR tyrosine kinase inhibitor gefitinib in esophageal tumor cells with a high polysomy for EGFR, suggesting a future role of anti-EGFR therapy for esophageal adenocarcinoma patients with a high EGFR polysomy.

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Acknowledgments

The authors thank Antje Heinecke for expert technical assistance.

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Authors and Affiliations

  1. Department of General, Visceral, Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Astrid Drenckhan, Anna Dupree, Thorsten Dohrmann, Oliver Mann, Jakob R. Izbicki & Stephanie J. Gros

  2. Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Tobias Grob

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  1. Astrid Drenckhan
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Correspondence to Stephanie J. Gros.

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Authors’ contribution

Study conception and design: Stephanie J. Gros, Astrid Drenckhan

Acquisition of data: Stephanie J. Gros, Astrid Drenckhan, Tobias Grob, Anna Dupree, Oliver Mann

Analysis and interpretation of data: Astrid Drenckhan, Stephanie J. Gros, Tobias Grob, Thorsten Dohrmann

Drafting of manuscript: Astrid Drenckhan, Stephanie J. Gros

Critical revision of manuscript: Tobias Grob, Jakob R. Izbicki

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Drenckhan, A., Grob, T., Dupree, A. et al. Esophageal carcinoma cell line with high EGFR polysomy is responsive to gefitinib. Langenbecks Arch Surg 399, 879–888 (2014). https://doi.org/10.1007/s00423-014-1235-1

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