title: Epidermal growth factor receptor (EGFR) is an independent adverse prognostic factor in esophageal adenocarcinoma patients treated with cisplatin-based neoadjuvant chemotherapy.
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.
authors.affiliation: Research Unit Analytical Pathology- Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, Neuherberg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Aichler
authors.affiliation: Research Unit Analytical Pathology- Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, Neuherberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Motschmann
authors.affiliation: Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, Neuherberg, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Jütting
authors.affiliation: Institute of Pathology, Technische Universität München, Trogerstraße 18, München, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Luber
authors.affiliation: Institute of Pathology, Technische Universität München, Trogerstraße 18, München, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Becker
authors.affiliation: Department of Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Ott
authors.affiliation: University Cancer Center Leipzig, University Clinic Leipzig, Liebigstraße 20, Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lordick
authors.affiliation: Institute of Pathology, Technische Universität München, Trogerstraße 18, München, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, München, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Feith
authors.affiliation: Directorate, University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany.
authors.forename: Jörg Rüdiger
authors.initials: JR
authors.lastname: Siewert
authors.affiliation: Research Unit Analytical Pathology- Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, Neuherberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000601:surgery; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000601:surgery; D005472:Fluorouracil / Q000008:administration & dosage; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D002955:Leucovorin / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil