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