Elevated levels of proliferating and recently migrated tumor-associated macrophages confer increased aggressiveness and worse outcomes in breast cancer

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 tumorassociated 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.