Estrogen receptor co-activator (AIB1) protein expression by automated quantitative analysis (AQUA) in a breast cancer tissue microarray and association with patient outcome

Malini Harigopal, Jonas Heymann, Sriparna Ghosh, Valsamo Anagnostou, Robert L. Camp, David L. Rimm

Research output: Contribution to journalArticle

Abstract

Purpose Amplified in breast cancer (AIB1 or SRC-3) is an estrogen receptor coregulatory protein that together with other co-activators like transcription intermediary factor 2 (TIF2) and nuclear receptor co-repressor (NCoR), is implicated in estrogen signaling pathway and estrogen regulated tumor progression. We investigated the prognostic significance of AIB1, TIF2 & NCoR protein expression breast tissue microarray (TMA), and studied the relationship of coregulatory proteins to prognostic biomarkers like estrogen (ER), progesterone (PR) & HER2/neu and between coregulatory proteins. Methods: AIBI, TIF2 & NCoR were studied by fluorescent immunohistochemical staining of a TMA with 670 breast cancer specimens, using AQUA software. Result: Using Cox univariate survival analyses, high AIB1 expression was associated with poor patient outcome (P = 0.002), while no association was noted for TIF2 (P = 0.376) & NCoR (P = 0.12). When subclassified by nodal or ER status, AIB1 was not prognostic in the node positive and ER positive subsets. However, in the ER negative and node negative subsets, high AIB1 expression was associated with poor patient outcome (P = 0.02 and P = 0.007 respectively). AIB1 retained its independent association with survival by multivariate analyses (P = 0.028). There was significant positive correlation between AIB1 and ER and PR status and with other cofators (TIF2 and NCoR) but not with HER2/neu status. Conclusion: High AIB1 expression was predictive of worse overall survival in our study, suggesting that AIB1 may be critical in breast carcinogenesis.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalBreast Cancer Research and Treatment
Volume115
Issue number1
DOIs
StatePublished - May 2009
Externally publishedYes

Fingerprint

Nuclear Receptor Coactivator 2
Co-Repressor Proteins
Estrogen Receptors
Estrogens
Breast Neoplasms
Proteins
Survival Analysis
Progesterone
Breast
Carcinogenesis
Software
Multivariate Analysis
Biomarkers
Staining and Labeling
Survival

Keywords

  • Breast cancer
  • Coactivator AIB1
  • Estrogen receptor
  • Prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Estrogen receptor co-activator (AIB1) protein expression by automated quantitative analysis (AQUA) in a breast cancer tissue microarray and association with patient outcome. / Harigopal, Malini; Heymann, Jonas; Ghosh, Sriparna; Anagnostou, Valsamo; Camp, Robert L.; Rimm, David L.

In: Breast Cancer Research and Treatment, Vol. 115, No. 1, 05.2009, p. 77-85.

Research output: Contribution to journalArticle

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abstract = "Purpose Amplified in breast cancer (AIB1 or SRC-3) is an estrogen receptor coregulatory protein that together with other co-activators like transcription intermediary factor 2 (TIF2) and nuclear receptor co-repressor (NCoR), is implicated in estrogen signaling pathway and estrogen regulated tumor progression. We investigated the prognostic significance of AIB1, TIF2 & NCoR protein expression breast tissue microarray (TMA), and studied the relationship of coregulatory proteins to prognostic biomarkers like estrogen (ER), progesterone (PR) & HER2/neu and between coregulatory proteins. Methods: AIBI, TIF2 & NCoR were studied by fluorescent immunohistochemical staining of a TMA with 670 breast cancer specimens, using AQUA software. Result: Using Cox univariate survival analyses, high AIB1 expression was associated with poor patient outcome (P = 0.002), while no association was noted for TIF2 (P = 0.376) & NCoR (P = 0.12). When subclassified by nodal or ER status, AIB1 was not prognostic in the node positive and ER positive subsets. However, in the ER negative and node negative subsets, high AIB1 expression was associated with poor patient outcome (P = 0.02 and P = 0.007 respectively). AIB1 retained its independent association with survival by multivariate analyses (P = 0.028). There was significant positive correlation between AIB1 and ER and PR status and with other cofators (TIF2 and NCoR) but not with HER2/neu status. Conclusion: High AIB1 expression was predictive of worse overall survival in our study, suggesting that AIB1 may be critical in breast carcinogenesis.",
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AU - Heymann, Jonas

AU - Ghosh, Sriparna

AU - Anagnostou, Valsamo

AU - Camp, Robert L.

AU - Rimm, David L.

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AB - Purpose Amplified in breast cancer (AIB1 or SRC-3) is an estrogen receptor coregulatory protein that together with other co-activators like transcription intermediary factor 2 (TIF2) and nuclear receptor co-repressor (NCoR), is implicated in estrogen signaling pathway and estrogen regulated tumor progression. We investigated the prognostic significance of AIB1, TIF2 & NCoR protein expression breast tissue microarray (TMA), and studied the relationship of coregulatory proteins to prognostic biomarkers like estrogen (ER), progesterone (PR) & HER2/neu and between coregulatory proteins. Methods: AIBI, TIF2 & NCoR were studied by fluorescent immunohistochemical staining of a TMA with 670 breast cancer specimens, using AQUA software. Result: Using Cox univariate survival analyses, high AIB1 expression was associated with poor patient outcome (P = 0.002), while no association was noted for TIF2 (P = 0.376) & NCoR (P = 0.12). When subclassified by nodal or ER status, AIB1 was not prognostic in the node positive and ER positive subsets. However, in the ER negative and node negative subsets, high AIB1 expression was associated with poor patient outcome (P = 0.02 and P = 0.007 respectively). AIB1 retained its independent association with survival by multivariate analyses (P = 0.028). There was significant positive correlation between AIB1 and ER and PR status and with other cofators (TIF2 and NCoR) but not with HER2/neu status. Conclusion: High AIB1 expression was predictive of worse overall survival in our study, suggesting that AIB1 may be critical in breast carcinogenesis.

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KW - Estrogen receptor

KW - Prognosis

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