| Summary: | <p>Abstract</p> <p>Background</p> <p>Tumor associated macrophages (TAMs) are alternatively activated macrophages that enhance tumor progression by promoting tumor cell invasion, migration and angiogenesis. TAMs have an anti-inflammatory function resembling M2 macrophages. CD163 is regarded as a highly specific monocyte/macrophage marker for M2 macrophages. In this study we evaluated the specificity of using the M2 macrophage marker CD163 as a TAM marker and compared its prognostic value with the more frequently used pan-macrophage marker CD68. We also analyzed the prognostic value of the localization of CD163<sup>+</sup> and CD68<sup>+</sup> myeloid cells in human breast cancer.</p> <p>Methods</p> <p>The extent of infiltrating CD163<sup>+</sup> or CD68<sup>+</sup> myeloid cells in tumor nest versus tumor stroma was evaluated by immunohistochemistry in tissue microarrays with tumors from 144 breast cancer cases. Spearman’s Rho and χ<sup>2</sup> tests were used to examine the correlations between CD163<sup>+</sup> or CD68<sup>+</sup> myeloid cells and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the impact of CD163<sup>+</sup> and CD68<sup>+</sup> myeloid cells in tumor stroma and tumor nest, respectively, on recurrence free survival, breast cancer specific and overall survival.</p> <p>Results</p> <p>We found that infiltration of CD163<sup>+</sup> and CD68<sup>+</sup> macrophages into tumor stroma, but not into tumor nest, were of clinical relevance. CD163<sup>+</sup> macrophages in tumor stroma positively correlated with higher grade, larger tumor size, Ki67 positivity, estrogen receptor negativity, progesterone receptor negativity, triple-negative/basal-like breast cancer and inversely correlated with luminal A breast cancer. Some CD163<sup>+</sup> areas lacked CD68 expression, suggesting that CD163 could be used as a general anti-inflammatory myeloid marker with prognostic impact. CD68<sup>+</sup> macrophages in tumor stroma positively correlated to tumor size and inversely correlated to luminal A breast cancer. More importantly, CD68 in tumor stroma was an independent prognostic factor for reduced breast cancer specific survival.</p> <p>Conclusion</p> <p>These findings highlight the importance of analyzing the localization rather than merely the presence of TAMs as a prognostic marker for breast cancer patients.</p>
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