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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2014

01-06-2014 | Preclinical study

Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study

Authors: Mohammed A. Aleskandarany, Ola H. Negm, Andrew R. Green, Mohamed A. H. Ahmed, Christopher C. Nolan, Patrick J. Tighe, Ian O. Ellis, Emad A. Rakha

Published in: Breast Cancer Research and Treatment | Issue 2/2014

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Abstract

Epithelial mesenchymal transition (EMT), as defined by loss of epithelial characteristics and gain of a mesenchymal phenotype, has been reported in vivo although the occurrence of events remains unclear. This study aims at exploration of EMT portraits of breast cancer (BC) with relevance to different molecular pathways, especially potential EMT triggers and BC molecular subtypes. Immunohistochemical (IHC) expression of markers/triggers of EMT was studied on a well-defined cohort of invasive non-lobular BC (n = 1,035), prepared as tissue microarrays. IHC panel of biomarkers included cadherins (cad; E-cad and N-cad), TGFβ1, PIK3CA, pAkt, and others. Reverse phase protein array (RPPA) was performed for quantitative analysis of proteins extracted from formalin fixed paraffin embedded tissues of a subset of cases from this cohort. Four combinatorial phenotypic groups representing cadherin switch were defined, including E-cad+/N-cad−, E-cad−/N-cad−, E-cad+/N-cad+, and E-cad−/N-cad+. Statistically significant association was noticed between these phenotypes and histological tumour grade, tumour type and size and NPI staging classes. The E-cad/N-cad switch occurred more frequently in the triple negative molecular class, both basal and non-basal, and in the HER2+ subtype than in luminal BC. Significant outcome differences were observed between cadherin switch combinatorial groups regarding BCSS and DMFS (p < 0.001). Results of RPPA confirm those observed using IHC regarding differential expressions of EMT markers/triggers. EMT/cadherin switch programs in BC appear to occur in synergy with TGFβ1 and PIK3/Akt pathways activation. These data explain, at translational proteomic level, the molecular heterogeneity and in turn the varied clinical behaviour of BC molecular subtypes. RPPA is a promising high-throughput technique in monitoring subtle quantitative changes in protein expression in archival material.
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Metadata
Title
Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study
Authors
Mohammed A. Aleskandarany
Ola H. Negm
Andrew R. Green
Mohamed A. H. Ahmed
Christopher C. Nolan
Patrick J. Tighe
Ian O. Ellis
Emad A. Rakha
Publication date
01-06-2014
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2014
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-014-2927-5

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