Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome (original) (raw)

Abstract

Macrophages, a key cell in the inflammatory cascade, have been associated with poor prognosis in cancers, including breast cancer. In this study, we investigated the relationship of a subset of macrophages—proliferating macrophages (promacs)—with clinico-pathologic characteristics of breast cancer, including tumor size, grade, stage, lymph node metastases, hormone receptor status, subtype, as well as early recurrence, and survival. This study included a discovery and validation set that was conducted at two institutions and laboratories (University of California, San Francisco and University of Chicago) using two independent cohorts of patients with breast cancer. Formalin-fixed, paraffin-embedded sections and/or tissue microarrays were double-stained with anti-CD68 (a macrophage marker) and anti-PCNA (a proliferation marker) antibodies. The presence of intratumoral promacs was significantly correlated with high grade, hormone receptor negative tumors, and a basal-like subtype. In contrast, there was no correlation between promacs and tumor size, stage, or the number of the involved lymph nodes. These findings were consistent between the two study cohorts. Finally, promac numbers were a significant predictor of recurrence and survival. In the pooled analysis, elevated promac levels were associated with a 77% increased risk of dying (P = 0.015). The presence of promacs in human breast cancer may serve as a prognostic indicator for poor outcomes and early recurrence and serve as a potential cellular target for novel therapeutic interventions.

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Acknowledgments

This study was supported by the Breast Cancer Research Foundation, the National Cancer Institute (grants CA-RO1 89085-01A, P50-CA58223-09A1, P50 CA125183, P50 ES012382, and P30 CA14599-32), the UC SPORE, and the Avon Foundation.

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Authors and Affiliations

  1. Department of Surgery, University of California, San Francisco, USA
    Michael J. Campbell, Elisabeth R. Garwood, Amy Lin & Laura J. Esserman
  2. Pritzker School of Medicine, University of Chicago, Chicago, USA
    Nathan Y. Tonlaar
  3. Department of Health Studies, University of Chicago, Chicago, USA
    Dezheng Huo
  4. Department of Epidemiology and Biostatistics, University of California, San Francisco, USA
    Dan H. Moore
  5. Department of Medicine, University of Chicago, Chicago, USA
    Andrey I. Khramtsov, Yinghua Chen, David O. Malaka, Oyinlolu O. Adeyanju & Olufunmilayo I. Olopade
  6. Department of Pathology, University of California, San Francisco, USA
    Afred Au & Frederick Baehner
  7. Department of Pathology, University of Chicago, Chicago, USA
    Shihong Li & Can Gong
  8. Department of Laboratory Medicine and Medicine, San Francisco General Hospital, University of California, San Francisco, USA
    Michael McGrath
  9. Carol F. Buck Breast Care Center, 1600 Divisadero St, Box 1710, San Francisco, CA, 94115, USA
    Laura J. Esserman

Authors

  1. Michael J. Campbell
  2. Nathan Y. Tonlaar
  3. Elisabeth R. Garwood
  4. Dezheng Huo
  5. Dan H. Moore
  6. Andrey I. Khramtsov
  7. Afred Au
  8. Frederick Baehner
  9. Yinghua Chen
  10. David O. Malaka
  11. Amy Lin
  12. Oyinlolu O. Adeyanju
  13. Shihong Li
  14. Can Gong
  15. Michael McGrath
  16. Olufunmilayo I. Olopade
  17. Laura J. Esserman

Corresponding author

Correspondence toLaura J. Esserman.

Additional information

Michael J. Campbell, Nathan Y. Tonlaar contributed equally to this work.

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Campbell, M.J., Tonlaar, N.Y., Garwood, E.R. et al. Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome.Breast Cancer Res Treat 128, 703–711 (2011). https://doi.org/10.1007/s10549-010-1154-y

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