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Apolipoprotein D predicts adverse outcome in women ≥70 years with operable breast cancer

Breast Cancer Research and Treatment volume 113, pages 519–528 (2009)Cite this article

Abstract

Apolipoprotein D (ApoD) is a lipocalin involved in various cellular processes, including cytoprotection. We retrospectively evaluated its prognostic impact in 272 women (median age 63 (range 21–89) years, with operable breast cancer (Stage I or IIa) treated according to national guidelines, stratified by age and menopausal status, with a median long-term follow-up of 12 years. ApoD, estrogen receptor-alpha (ERα), and progesterone receptor (PR) positivity were determined by quantitative immunohistochemistry in tissue microarrays taken from the invasive front of the tumors and in whole tumor sections. ApoD was expressed in 50% of the tumors. Diffuse nuclear and cytoplasmic (ApoDCN), but not granular cytoplasmic ApoD expression in the invasive front was a detrimental factor for elderly patients over 70 years of age, (n = 83), but not for younger and pre-menopausal patients. ApoDCN expression correlated with lymph node metastases (P = 0.04). Moreover, a correlation between ApoDCN localization and age over 70 years was observed (P = 0.03). In the elderly, ApoDCN positive tumors had both a significantly shorter relapse-free survival (all locations) (P = 0.02) and a decreased breast cancer-specific survival (P < 0.0001). Moreover, the prognostic importance of ApoD was dose dependent (P = 0.002) Multivariate analysis confirmed the prognostic value of ApoDCN. When the elderly patients were stratified by nodal status, ApoD showed prognostic importance only in the node positive patients (n = 30) (HR = 9.6; 95% CI = 2.3–40.4). The potential relevance of ApoD in this increasingly frequent group of breast cancer patients should be further explored.

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Acknowledgements

Dr. Håvard Søiland, MD, is a Research Fellow, financially sponsored by the Western Norwegian Health Authorities (project # 911166). Financial support from The Norwegian Cancer Society, The L. Meltzer Foundation, and O. Mjålands Foundation is highly appreciated. We are grateful for the technical assistance of Britt Fjæran.

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Affiliations

  1. Department of Surgery, Stavanger University Hospital, 4068, Stavanger, Norway

    Håvard Søiland, Hartwig Kørner & Jon Arne Søreide

  2. Department of Surgical Sciences, University of Bergen, Bergen, Norway

    Håvard Søiland, Hartwig Kørner, Jan Erik Varhaug & Jon Arne Søreide

  3. Department of Pathology, Stavanger University Hospital, Stavanger, Norway

    Emiel A. M. Janssen, Ivar Skaland, Einar Gudlaugsson & Jan P. A. Baak

  4. Section for Endocrine and Breast Surgery, Haukeland University Hospital, Bergen, Norway

    Jan Erik Varhaug

  5. The Gade Institute, University of Bergen, Bergen, Norway

    Jan P. A. Baak

  6. Free University, Amsterdam, The Netherlands

    Jan P. A. Baak

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  1. Håvard Søiland
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  2. Emiel A. M. Janssen
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Correspondence to Jon Arne Søreide.

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Søiland, H., Janssen, E.A.M., Kørner, H. et al. Apolipoprotein D predicts adverse outcome in women ≥70 years with operable breast cancer. Breast Cancer Res Treat 113, 519–528 (2009). https://doi.org/10.1007/s10549-008-9955-y

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  • DOI: https://doi.org/10.1007/s10549-008-9955-y

Keywords

  • Apolipoprotein D
  • Elderly patients
  • Prognosis
  • Operable breast cancer