In situ detection of HER2:HER2 and HER2:HER3 protein–protein interactions demonstrates prognostic significance in early breast cancer

HER2 overexpression/amplification is linked with poor prognosis in early breast cancer. Co-expression of HER2 and HER3 is associated with endocrine and chemotherapy resistance, driven not simply by expression but by signalling via HER2:HER3 or HER2:HER2 dimers. Proximity ligation assays (PLAs) detec...

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Bibliographic Details
Published in:Breast cancer research and treatment 2012-04, Vol.132 (2), p.463-470
Main Authors: Spears, Melanie, Taylor, Karen J., Munro, Alison F., Cunningham, Carrie A., Mallon, Elizabeth A., Twelves, Chris J., Cameron, David A., Thomas, Jeremy, Bartlett, John M. S.
Format: Article
Language:English
Subjects:
Analysis
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Breast cancer
Breast Neoplasms - chemistry
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Cancer
Cancer research
Cancer therapies
Chemotherapy
Digital integrated circuits
Disease-Free Survival
Female
Gene Amplification
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Kaplan-Meier Estimate
Mammary gland diseases
Medical prognosis
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Multivariate Analysis
Neoplasm Staging
Oncology
Preclinical Study
Prognosis
Proportional Hazards Models
Protein Interaction Domains and Motifs
Protein Interaction Mapping
Protein Multimerization
Proteins
Randomized Controlled Trials as Topic
Receptor, ErbB-2 - analysis
Receptor, ErbB-2 - genetics
Receptor, ErbB-3 - analysis
Receptor, ErbB-3 - genetics
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
Tumors
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Summary:HER2 overexpression/amplification is linked with poor prognosis in early breast cancer. Co-expression of HER2 and HER3 is associated with endocrine and chemotherapy resistance, driven not simply by expression but by signalling via HER2:HER3 or HER2:HER2 dimers. Proximity ligation assays (PLAs) detect protein–protein complexes at a single-molecule level and allow study of signalling pathways in situ. A cohort of 100 tumours was analyzed by PLA, IHC and FISH. HER complexes were analyzed by PLA in a further 321 tumours from the BR9601 trial comparing cyclophosphamide, methotrexate and fluorouracil (CMF) with epirubicin followed by CMF (epi-CMF). The relationships between HER dimer expression and RFS and OS were investigated, and multivariate regression analysis identified factors influencing patient prognosis. PLA successfully and reproducibly detected HER2:HER2 and HER2:HER3 protein complexes in vivo. A significant association ( P  
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-011-1606-z