title: Prognostic relevance of AIB1 (NCoA3) amplification and overexpression in breast cancer.
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.
authors: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany. e.burandt@uke.de
authors: E
authors: E
authors: Burandt
authors: G
authors: G
authors: Jens
authors: F
authors: F
authors: Holst
authors: F
authors: F
authors: Jänicke
authors: V
authors: V
authors: Müller
authors: A
authors: A
authors: Quaas
authors: M
authors: M
authors: Choschzick
authors: W
authors: W
authors: Wilczak
authors: L
authors: L
authors: Terracciano
authors: R
authors: R
authors: Simon
authors: G
authors: G
authors: Sauter
authors: A
authors: A
authors: Lebeau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis
chemical_list: D019394:Ki-67 Antigen; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3