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

Abstract

UNLABELLED:

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.

• Authors: E Burandt, G Jens, F Holst, F Jänicke, V Müller, A Quaas, M Choschzick, W Wilczak, L Terracciano, R Simon, G Sauter, A Lebeau
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 137 Issue 3 Pg. 745-53 (Feb 2013) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 23322234 (Publication Type: Journal Article)

Chemical References

• Ki-67 Antigen
• NCOA3 protein, human
• Nuclear Receptor Coactivator 3

Topics

• Adult
• Aged
• Aged, 80 and over
• Breast Neoplasms (genetics, metabolism, mortality, pathology)
• Female
• Gene Amplification
• Gene Dosage
• Gene Expression
• Humans
• Ki-67 Antigen (metabolism)
• Middle Aged
• Nuclear Receptor Coactivator 3 (genetics, metabolism)
• Prognosis