title: Interaction Between Beta-Catenin and EGFR Expression by Immunohistochemistry Identifies Prognostic Subgroups in Early High-risk Triple-negative Breast Cancer.
abstract: Wnt and epidermal growth factor receptor (EGFR) pathway abnormalities and de-stabilization of cell adhesion are all important aspects of the pathogenesis of triple-negative breast cancer (TNBC). Herein we investigated how the expression of related protein markers may affect the outcome of patients bearing TNBC treated in the adjuvant setting. Immunohistochemistry for beta-catenin, Myc (Wnt pathway), E-cadherin, P-cadherin (cell-adhesion), EGFR and cytokeratin 5 (CK5) (identification of basal-like tumors) was carried out in 364 centrally confirmed TNBCs. Survival analysis was performed with Cox-regression models according to dichotomized continuous protein expression data and marker interactions. In 352 evaluable tumors, 81.5% were basal-like TNBC. E-cadherin and P-cadherin were positively associated, with co-expression being present in 68% of tumors. Individual markers did not affect patient outcome. However, a statistically significant interaction was shown such that low expression of beta-catenin in the cell membrane, defined as expression below the median of the H-score distribution, was associated with unfavourable disease-free survival among tumors that expressed EGFR, but not in the absence of EGFR expression (interaction p=0.0085). The interaction persisted after correcting for clinicopathological variables. A considerable number of TNBC co-expresses E-cadherin and P-cadherin, while membranous localization of beta-catenin may predict patient outcome in an EGFR-dependent manner. This novel interaction seems worthy for validating with regards to its biological and clinical relevance.
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece slakis@auth.gr.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Lakis
authors.affiliation: Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
authors.forename: Stefanos
authors.initials: S
authors.lastname: Dimoudis
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kotoula
authors.affiliation: Health Data Specialists Ltd., Athens, Greece.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Alexopoulou
authors.affiliation: Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kostopoulos
authors.affiliation: Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
authors.forename: Triantafyllia
authors.initials: T
authors.lastname: Koletsa
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Mattheos
authors.initials: M
authors.lastname: Bobos
authors.affiliation: Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Timotheadou
authors.affiliation: Department of Pathology, Alexandra Hospital, Athens, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Papaspirou
authors.affiliation: Department of Pathology, Papageorgiou Hospital, Thessaloniki, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Efstratiou
authors.affiliation: Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Aravantinos
authors.affiliation: Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Karavasilis
authors.affiliation: Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
authors.forename: Flora
authors.initials: F
authors.lastname: Zagouri
authors.affiliation: First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Gogas
authors.affiliation: Third Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Razis
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.affiliation: Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Christodoulou
authors.affiliation: Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D011485:Protein Binding; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin; D004815:Epidermal Growth Factor
keywords: EGFR; EMT; Myc; Triple-negative breast cancer (TNBC); Wnt pathway; beta-catenin immunohistochemistry