Oncotarget

Clinical Research Papers:

Epidermal growth factor receptor (EGFR) is an independent adverse prognostic factor in esophageal adenocarcinoma patients treated with cisplatin-based neoadjuvant chemotherapy

Michaela Aichler, Martin Motschmann, Uta Jütting, Birgit Luber, Karen Becker, Katja Ott, Florian Lordick, Rupert Langer, Marcus Feith, Jörg Rüdiger Siewert and Axel Walch _

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Oncotarget. 2014; 5:6620-6632. https://doi.org/10.18632/oncotarget.2268

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Abstract

Michaela Aichler1, Martin Motschmann1, Uta Jütting2, Birgit Luber3, Karen Becker3, Katja Ott4, Florian Lordick5, Rupert Langer3, Marcus Feith6, Jörg Rüdiger Siewert7 and Axel Walch1

1 Research Unit Analytical Pathology- Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, Neuherberg, Germany

2 Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, Neuherberg, Germany

3 Institute of Pathology, Technische Universität München, Trogerstraße 18, München, Germany

4 Department of Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, Germany

5 University Cancer Center Leipzig, University Clinic Leipzig, Liebigstraße 20, Leipzig, Germany

6 Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, München, Germany

7 Directorate, University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany

Correspondence:

Axel Walch, email:

Keywords: EGFR, prognosis, chemotherapy, cisplatin, esophageal cancer

Received: May 16, 2014 Accepted: July 26, 2014 Published: July 26, 2014

Abstract

Neoadjuvant platin-based therapy is accepted as a standard therapy for advanced esophageal adenocarcinoma (EAC). Patients who respond have a better survival prognosis, but still a significant number of responder patients die from tumor recurrence. Molecular markers for prognosis in neoadjuvantly treated EAC patients have not been identified yet. We investigated the epidermal growth factor receptor (EGFR) in prognosis and chemotherapy resistance in these patients. Two EAC patient cohorts, either treated by neoadjuvant cisplatin-based chemotherapy followed by surgery (n=86) or by surgical resection (n=46) were analyzed for EGFR protein expression and gene copy number. Data were correlated with clinical and histopathological response, disease-free and overall survival.

In case of EGFR overexpression, the prognosis for neoadjuvant chemotherapy responders was poor as in non-responders. Responders had a significantly better disease-free survival than non-responders only if EGFR expression level (p=0.0152) or copy number (p=0.0050) was low. Comparing neoadjuvantly treated patients and primary resection patients, tumors of non-responder patients more frequently exhibited EGFR overexpression, providing evidence that EGFR is a factor for indicating chemotherapy resistance.

EGFR overexpression and gene copy number are independent adverse prognostic factors for neoadjuvant chemotherapy-treated EAC patients, particularly for responders. Furthermore, EGFR overexpression is involved in resistance to cisplatin-based neoadjuvant chemotherapy.


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