Interaction Between Beta-Catenin and EGFR Expression by Immunohistochemistry Identifies Prognostic Subgroups in Early High-risk Triple-negative Breast Cancer

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 b...

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Bibliographic Details
Published in:Anticancer research 2016-05, Vol.36 (5), p.2365-2378
Main Authors: Lakis, Sotirios, Dimoudis, Stefanos, Kotoula, Vassiliki, Alexopoulou, Zoi, Kostopoulos, Ioannis, Koletsa, Triantafyllia, Bobos, Mattheos, Timotheadou, Eleni, Papaspirou, Irene, Efstratiou, Ioannis, Aravantinos, Gerasimos, Karavasilis, Vasilios, Zagouri, Flora, Gogas, Helen, Razis, Evangelia, Pentheroudakis, George, Christodoulou, Christos, Pectasides, Dimitrios, Fountzilas, George
Format: Article
Language:English
Subjects:
beta Catenin - metabolism
Epidermal Growth Factor - metabolism
Female
Humans
Immunohistochemistry
Middle Aged
Prognosis
Protein Binding
Triple Negative Breast Neoplasms - metabolism
Triple Negative Breast Neoplasms - pathology
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Summary: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.
ISSN:1791-7530