Prognostic relevance of AIB1 (NCoA3) amplification and overexpression in breast cancer.
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Prognostic relevance of AIB1 (NCoA3) amplification and overexpression in breast cancer. / Burandt, Eike Christian; Jens, G; Holst, Frederik; Jänicke, Fritz; Müller, Volkmar; Quaas, Alexander; Choschzick, Matthias; Wilczak, Waldemar; Terracciano, L; Simon, Ronald; Sauter, Guido; Lebeau, Annette.
In: BREAST CANCER RES TR, Vol. 137, No. 3, 3, 2013, p. 745-753.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Prognostic relevance of AIB1 (NCoA3) amplification and overexpression in breast cancer.
AU - Burandt, Eike Christian
AU - Jens, G
AU - Holst, Frederik
AU - Jänicke, Fritz
AU - Müller, Volkmar
AU - Quaas, Alexander
AU - Choschzick, Matthias
AU - Wilczak, Waldemar
AU - Terracciano, L
AU - Simon, Ronald
AU - Sauter, Guido
AU - Lebeau, Annette
PY - 2013
Y1 - 2013
N2 - AIB1 (amplified in breast cancer 1) is an estrogen receptor? (ER?) 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 ER?-positive and -negative disease are poorly understood. Therefore, we analyzed the clinical significance of AIB1 in breast cancer with respect to ER?-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 ER? 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 ER? co-activator. AIB1 has an impact on cell cycle regulation in ER?-positive as well as ER?-negative tumors. Furthermore, AIB1 amplification characterizes a subgroup of ER?-positive breast cancer with worse outcome. Therefore, AIB1 might be helpful to identify those ER?-positive breast cancers patients who are candidates for adjuvant chemotherapy.
AB - AIB1 (amplified in breast cancer 1) is an estrogen receptor? (ER?) 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 ER?-positive and -negative disease are poorly understood. Therefore, we analyzed the clinical significance of AIB1 in breast cancer with respect to ER?-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 ER? 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 ER? co-activator. AIB1 has an impact on cell cycle regulation in ER?-positive as well as ER?-negative tumors. Furthermore, AIB1 amplification characterizes a subgroup of ER?-positive breast cancer with worse outcome. Therefore, AIB1 might be helpful to identify those ER?-positive breast cancers patients who are candidates for adjuvant chemotherapy.
KW - Adult
KW - Humans
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Prognosis
KW - Gene Expression
KW - Gene Dosage
KW - Gene Amplification
KW - Ki-67 Antigen/metabolism
KW - Breast Neoplasms/genetics/metabolism/mortality/pathology
KW - Nuclear Receptor Coactivator 3/genetics/metabolism
KW - Adult
KW - Humans
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Prognosis
KW - Gene Expression
KW - Gene Dosage
KW - Gene Amplification
KW - Ki-67 Antigen/metabolism
KW - Breast Neoplasms/genetics/metabolism/mortality/pathology
KW - Nuclear Receptor Coactivator 3/genetics/metabolism
M3 - SCORING: Journal article
VL - 137
SP - 745
EP - 753
JO - BREAST CANCER RES TR
JF - BREAST CANCER RES TR
SN - 0167-6806
IS - 3
M1 - 3
ER -
