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01.02.2013 | Preclinical study

Prognostic relevance of AIB1 (NCoA3) amplification and overexpression in breast cancer

verfasst von: E. Burandt, G. Jens, F. Holst, F. Jänicke, V. Müller, A. Quaas, M. Choschzick, W. Wilczak, L. Terracciano, R. Simon, G. Sauter, A. Lebeau

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2013

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Abstract

AIB1 (amplified in breast cancer 1) is an estrogen receptorα (ERα) co-activator, known to be amplified and overexpressed in a fraction of breast cancers. It has been linked to prognosis and tamoxifen resistance. However, results have been ambiguous. The different functions of AIB1 in ERα-positive and -negative disease are poorly understood. Therefore, we analyzed the clinical significance of AIB1 in breast cancer with respect to ERα-status and characterized the subgroups. 2,197 breast carcinomas sampled on a pre-existing tissue microarray (TMA) were analyzed for AIB1 expression and amplification by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results: AIB1 expression was detected in 60 % of the tumors. It was associated with tumor size (p = 0.003), high histological grade (p < 0.0001), poor disease-specific, and overall survival (p = 0.0018 and p = 0.003). There was a strong inverse relationship between AIB1 and ERα expression (p < 0.0001). AIB1 overexpression was associated with increased Ki67 labeling index (p < 0.0001), even if analyzed for different ER expression levels. AIB1 amplification was found in 11 % of the carcinomas. It was associated with high histological grade (p = 0.0012), lymph node involvement (p = 0.0163), and poor disease-specific survival (p = 0.0032) but not with overall survival (p = 0.1672) or ER status (p = 0.4456). If ER-positive tumors were stratified according to their AIB1 amplification status, there was a significant worse disease-specific survival in cases showing AIB1 amplification (p = 0.0017). AIB1 expression is associated with unfavorable prognosis and tumor phenotype. It seems to unfold its oncogenic potential at least in part independent from its role as an ERα co-activator. AIB1 has an impact on cell cycle regulation in ERα-positive as well as ERα-negative tumors. Furthermore, AIB1 amplification characterizes a subgroup of ERα-positive breast cancer with worse outcome. Therefore, AIB1 might be helpful to identify those ERα-positive breast cancers patients who are candidates for adjuvant chemotherapy.

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Titel: Prognostic relevance of AIB1 (NCoA3) amplification and overexpression in breast cancer
verfasst von: E. Burandt
G. Jens
F. Holst
F. Jänicke
V. Müller
A. Quaas
M. Choschzick
W. Wilczak
L. Terracciano
R. Simon
G. Sauter
A. Lebeau
Publikationsdatum: 01.02.2013
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2013
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-013-2406-4

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Prognostic relevance of AIB1 (NCoA3) amplification and overexpression in breast cancer

Abstract

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