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Elevated Levels of Proliferating and Recently Migrated Tumor-associated Macrophages Confer Increased Aggressiveness and Worse Outcomes in Breast Cancer

  • Translational Research and Biomarkers
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Abstract

Purpose

Macrophages play a major role in inflammatory processes and have been associated with poor prognosis in a variety of cancers, including breast cancer. Previously, we investigated the relationship of a subset of tumor-associated macrophages (PCNA+ TAMs) with clinicopathologic characteristics of breast cancer. We reported that high PCNA+ TAM counts were associated with hormone receptor (HR)-negative, high-grade tumors and early recurrence. To further understand the significance of elevated PCNA+ TAMs and the functionality of TAMs, we examined the expression of S100A8/S100A9 with the antibody Mac387. The heterodimeric S100A8/S100A9 complex plays a role in inflammation and is increased in several cancer types.

Methods

We performed immunohistochemistry using the Mac387 antibody on 367 invasive human breast cancer cases. Results were compared to previous PCNA+ TAM counts and were correlated with patient outcomes adjusting for HR status and histologic grade.

Results

Like PCNA+ TAMs, high Mac387 counts were associated with HR negativity, high tumor grade, younger age, and decreased recurrence-free survival. Mac387, however, appears to identify both a subset of macrophages and a subset of tumor cells. The concordance between Mac387 and PCNA+ TAM counts was low and cases that had both high Mac387 and high PCNA+ TAMs counts had a stronger association with early recurrence.

Conclusions

The presence of high numbers of PCNA+ TAMs and Mac387-positive cells in breast cancers with poor outcomes may implicate a subset of TAMs in breast cancer pathogenesis, and may ultimately serve to develop potential cellular targets for therapeutic interventions.

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Acknowledgment

This work was supported by the California Breast Cancer Research Program Postdoctoral fellowship 15FB-0108 (RAM), the Director of the Office of Biological and Environmental Research, U.S. Department of Energy contract DE-AC02-05CH11231, and by the National Institutes of Health, National Cancer Institute, grant P50 CA 58207 (JWG).

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Authors and Affiliations

  1. Department of Surgery, University of California, San Francisco, CA, USA

    Rita A. Mukhtar MD, Vickram J. Tandon BS, Onouwem Nseyo BA, Patrick Twomey MD, Alfred Au MD, Michael J. Campbell PhD & Laura J. Esserman MD, MBA

  2. Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, CA, USA

    Amy P. Moore MD

  3. Department of Surgery, Abia State University, Abia, Nigeria

    Charles Adeyinka Adisa MBBS & Ndukauba Eleweke MBBS

  4. Departments of Laboratory Medicine and Pathology, University of California, San Francisco, CA, USA

    Frederick L. Baehner MD & Michael S. McGrath MD, PhD

  5. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    Dan H. Moore PhD

  6. Department of Medicine, Division of Hematology and Oncology, University of Chicago, Chicago, IL, USA

    Olofunmilayo I. Olopade MD

  7. Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA

    Joe W. Gray PhD

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  1. Rita A. Mukhtar MD
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Corresponding author

Correspondence to Laura J. Esserman MD, MBA.

Additional information

Michael J. Campbel and Laura J. Esserman contributed equally to this work, and both should be considered senior author.

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Mukhtar, R.A., Moore, A.P., Tandon, V.J. et al. Elevated Levels of Proliferating and Recently Migrated Tumor-associated Macrophages Confer Increased Aggressiveness and Worse Outcomes in Breast Cancer. Ann Surg Oncol 19, 3979–3986 (2012). https://doi.org/10.1245/s10434-012-2415-2

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  • DOI: https://doi.org/10.1245/s10434-012-2415-2

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