Annals of Surgical Oncology

, Volume 19, Issue 12, pp 3979–3986

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

  • Rita A. Mukhtar
  • Amy P. Moore
  • Vickram J. Tandon
  • Onouwem Nseyo
  • Patrick Twomey
  • Charles Adeyinka Adisa
  • Ndukauba Eleweke
  • Alfred Au
  • Frederick L. Baehner
  • Dan H. Moore
  • Michael S. McGrath
  • Olofunmilayo I. Olopade
  • Joe W. Gray
  • Michael J. Campbell
  • Laura J. Esserman
Translational Research and Biomarkers

DOI: 10.1245/s10434-012-2415-2

Cite this article as:
Mukhtar, R.A., Moore, A.P., Tandon, V.J. et al. Ann Surg Oncol (2012) 19: 3979. doi:10.1245/s10434-012-2415-2
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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.

Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Rita A. Mukhtar
    • 1
  • Amy P. Moore
    • 2
  • Vickram J. Tandon
    • 1
  • Onouwem Nseyo
    • 1
  • Patrick Twomey
    • 1
  • Charles Adeyinka Adisa
    • 3
  • Ndukauba Eleweke
    • 3
  • Alfred Au
    • 1
  • Frederick L. Baehner
    • 4
  • Dan H. Moore
    • 5
  • Michael S. McGrath
    • 4
  • Olofunmilayo I. Olopade
    • 6
  • Joe W. Gray
    • 7
  • Michael J. Campbell
    • 1
  • Laura J. Esserman
    • 1
  1. 1.Department of SurgeryUniversity of CaliforniaSan FranciscoUSA
  2. 2.Department of Medicine, Division of Hematology and OncologyUniversity of CaliforniaSan FranciscoUSA
  3. 3.Department of SurgeryAbia State UniversityAbiaNigeria
  4. 4.Departments of Laboratory Medicine and PathologyUniversity of CaliforniaSan FranciscoUSA
  5. 5.Department of Epidemiology and BiostatisticsUniversity of CaliforniaSan FranciscoUSA
  6. 6.Department of Medicine, Division of Hematology and OncologyUniversity of ChicagoChicagoUSA
  7. 7.Department of Biomedical EngineeringOregon Health and Science UniversityPortlandUSA