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FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer

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Abstract

Oestrogen receptor (ER)-positive breast cancer (BC) constitutes a heterogeneous group of tumours with regard to outcome and response to therapy. Accurate stratification of ER-positive BC according to risk of relapse and response to therapy will be achieved through an improved understanding of ER and ER-related biological pathways. Recent studies have identified Forkhead box O3a (FOXO3a) transcription factor as an intracellular mediator of ERα expression and as an important downstream target of the Akt/PI3K pathway indicating a biological and potential clinical role for FOXO3a in ER-positive BC. In this study, we investigated the clinical relevance and biological associations of FOXO3a protein expression, using tissue microarrays and immunohistochemistry, in a large series of patients with invasive breast cancer. FOXO3a protein expression showed both nuclear and/or cytoplasmic staining patterns. FOXO3a predominant nuclear expression was positively associated with biomarkers of good prognosis including PgR, FOXA1 and p27 expression. There was an inverse association with mitotic counts, MIB1 growth fraction, C-MYC and PIK3CA expression. With respect to patient outcome, FOXO3a nuclear localisation was associated with longer BC specific survival (P < 0.001) and longer distant metastasis free interval (P = 0.001), independently of the well-established breast cancer prognostic factors. In conclusion, our results demonstrate the biological and prognostic role of FOXO3a protein expression and its subcellular localisation in ER-positive/luminal-like BC possibly through its involvement in controlling cell proliferation.

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Acknowledgments

We thank the Ministry of Higher Education (Egypt) for funding H. O. Habashy, M. Ahmed, M. Aleskandarany and E. Rakha.

Conflict of interest

None.

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Authors and Affiliations

  1. Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, NG7 2UH, UK

    Hany Onsy Habashy, Mohammed Aleskandarany, Mohamed AH Ahmed, Andrew R. Green & Ian O. Ellis

  2. Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura City, Egypt

    Hany Onsy Habashy

  3. Department of Pathology, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, NG5 1PB, UK

    Emad A. Rakha & Desmond G. Powe

  4. Department of Pathology, Menoufia University, Shibin el Kom, Egypt

    Mohammed Aleskandarany

  5. Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Mohamed AH Ahmed

  6. Department of Histopathology, Nottingham University Hospitals NHS Trust and University of Nottingham, Hucknall Road, Nottingham, NG5 1PB, UK

    Ian O. Ellis

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  1. Hany Onsy Habashy
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  2. Emad A. Rakha
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  3. Mohammed Aleskandarany
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  4. Mohamed AH Ahmed
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  6. Ian O. Ellis
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  7. Desmond G. Powe
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Corresponding author

Correspondence to Ian O. Ellis.

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Habashy, H.O., Rakha, E.A., Aleskandarany, M. et al. FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer. Breast Cancer Res Treat 129, 11–21 (2011). https://doi.org/10.1007/s10549-010-1161-z

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  • DOI: https://doi.org/10.1007/s10549-010-1161-z

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