CD68- and CD163-positive tumor infiltrating macrophages in non-metastatic breast cancer: a retrospective study and meta-analysis

Studies have indicated the significance of tumor associated macrophages (TAMs) in breast cancer; however, inconsistent results still exist. We retrospectively reviewed the macrophage distribution in 1579 breast cancer specimens with anti-CD68 or anti-CD163 immunohistochemical staining, and further analyzed the overall survival data. Furthermore, we performed a retrospective study and systematic review of the published studies on CD68- and CD163-positive macrophages in non-metastatic breast cancer. 13 studies with 5116 patients were included in this meta-analysis. Our own data revealed a high density of both CD68- and CD163-positive TAMs that was significantly related to lymph node metastasis (CD68, P = 0.003; CD163, P < 0.001); high Ki67 (CD68, P = 0.026; CD163, P < 0.001), poor histological grade (CD68, P < 0.001; CD163, P < 0.001) and hormonal receptor negativity (CD68, P < 0.001; CD163, P < 0.001); only CD163-positive TAMs were associated with poor overall survival (P = 0.003). Nonetheless, the meta-analysis only found that CD68- and CD163-positive TAMs were associated with high Ki67 [CD68, Relative risk (RR): 1.18, 95% confidence interval (CI): 1.09-1.28; CD163, RR: 1.75, 95% CI: 1.39-2.20], advanced histological grade (CD68, RR: 1.72, 95% CI: 1.46-2.03; CD163, RR: 1.99, 95% CI: 1.35-2.94) and low hormonal receptor levels (CD68, RR: 0.75, 95% CI: 0.69-0.82; CD163, RR: 0.82, 95% CI: 0.74-0.90), but not lymph node metastasis and HER2 expression. This meta-analysis further supports the clinical significance of TAMs in breast cancer, and both CD68- and CD163-positive TAMs could be prognostic markers in non-metastatic breast cancer.