• 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, and Laura J Esserman.
• Department of Surgery, University of California, San Francisco, CA, USA.
• Ann. Surg. Oncol. 2012 Nov 1; 19 (12): 3979-86.

PurposeMacrophages 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.MethodsWe 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.ResultsLike 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.ConclusionsThe 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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