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Mammary stem cell and macrophage markers are enriched in normal tissue adjacent to inflammatory breast cancer

  • Preclinical study
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Introduction

We hypothesized that breast tissue not involved by tumor in inflammatory breast cancer (IBC) patients contains intrinsic differences, including increased mammary stem cells and macrophage infiltration, which may promote the IBC phenotype.

Materials and methods

Normal breast parenchyma ≥ 5 cm away from primary tumors was obtained from mastectomy specimens. This included an initial cohort of 8 IBC patients and 60 non-IBC patients followed by a validation cohort of 19 IBC patients and 25 non-IBC patients. Samples were immunostained for either CD44+CD49f+CD133/2+ mammary stem cell markers or the CD68 macrophage marker and correlated with IBC status. Quantitation of positive cells was determined using inForm software from PerkinElmer. We also examined the association between IBC status and previously published tumorigenic stem cell and IBC tumor signatures in the validation cohort samples.

Results

8 of 8 IBC samples expressed isolated CD44+CD49f+CD133/2+ stem cell marked cells in the initial cohort as opposed to 0/60 non-IBC samples (p = 0.001). Similarly, the median number of CD44+CD49f+CD133/2+ cells was significantly higher in the IBC validation cohort as opposed to the non-IBC validation cohort (25.7 vs. 14.2, p = 0.007). 7 of 8 IBC samples expressed CD68 + histologically confirmed macrophages in initial cohort as opposed to 12/48 non-IBC samples (p = 0.001). In the validation cohort, the median number of CD68 + cells in IBC was 3.7 versus 1.0 in the non-IBC cohort (p = 0.06). IBC normal tissue was positively associated with a tumorigenic stem cell signature (p = 0.02) and with a 79-gene IBC signature (p < 0.001).

Conclusions

Normal tissue from IBC patients is enriched for both mammary stem cells and macrophages and has higher association with both a tumorigenic stem cell signature and IBC-specific tumor signature. Collectively, these data suggest that IBC normal tissue differs from non-IBC tissue. Whether these changes occur before the tumor develops or is induced by tumor warrants further investigation.

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Acknowledgements

Funding was provided by National Institutes of Health (Grant Nos. R01CA138239-01, 1R01CA180061-01)

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Authors and Affiliations

  1. Departments of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jay P. Reddy, Richard Larson, Daniel Smith, Arvind Bambhroliya & Wendy A. Woodward

  2. MD Anderson Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jay P. Reddy, Richard Larson, Daniel Smith, Bisrat G. Debeb, Arvind Bambhroliya & Wendy A. Woodward

  3. Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Rachel L. Atkinson & Abenaa M. Brewster

  4. Flow Cytometry and Cell Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jared K. Burks

  5. Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Brian Ruffell

  6. Department of Medicine and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Chad J. Creighton

  7. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    James M. Reuben

  8. Faculty of Medicine and Health Sciences, Center for Oncological Research, University of Antwerp, Antwerp, Belgium

    Steven J. Van Laere

  9. Department of Breast Surgical Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Savitri Krishnamurthy

  10. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    William F. Symmans

  11. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Chad J. Creighton

  12. Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, Unit 1202, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Wendy A. Woodward

Authors
  1. Jay P. Reddy
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  2. Rachel L. Atkinson
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  3. Richard Larson
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  5. Daniel Smith
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  6. Bisrat G. Debeb
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  9. Arvind Bambhroliya
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  10. James M. Reuben
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  12. Savitri Krishnamurthy
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  13. William F. Symmans
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  14. Abenaa M. Brewster
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  15. Wendy A. Woodward
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Corresponding author

Correspondence to Wendy A. Woodward.

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The authors have no conflict of interest to declare.

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Reddy, J.P., Atkinson, R.L., Larson, R. et al. Mammary stem cell and macrophage markers are enriched in normal tissue adjacent to inflammatory breast cancer. Breast Cancer Res Treat 171, 283–293 (2018). https://doi.org/10.1007/s10549-018-4835-6

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  • DOI: https://doi.org/10.1007/s10549-018-4835-6

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