Abstract
M2-like tumor-associated macrophages promote breast tumor growth and survival and may migrate into the peripheral blood. However, the frequency of circulating M2-like monocytes in the peripheral blood of breast cancer patients has not been clarified. The objective of this study was to determine the percentages of circulating M2-like monocytes in patients with breast cancer. Immunofluorescence staining for CD68 and CD163 was performed to detect M2-like macrophages in pathological tissues. Flow cytometry was used to assess the frequencies of circulating CD14+CD163+/CD14+CD204+/CD14+CD163+CD204+ M2-like monocytes in 99 breast cancer patients, 56 patients with benign breast disease, and 60 healthy controls. Receiver operating characteristic curve analysis was used to compare the diagnostic values of circulating M2-like monocytes, carcinoembryonic antigen, and cancer antigen 15-3. The associations among circulating M2-like monocytes and clinical breast cancer parameters were analyzed. The number of CD68+CD163+ M2-like macrophages was significantly higher in breast cancer tissues than in benign tissues. In the peripheral blood, CD14+CD163+/CD14+CD204+/CD14+CD163+CD204+ M2-like monocytes were elevated in breast cancer patients compared with normal controls and patients with benign breast disease. The area under the receiver operating curve for circulating CD14+CD163+CD204+ M2-like monocytes was 0.888 (95% confidence interval: 0.839-0.936), a value higher than those for carcinoembryonic antigen and cancer antigen 15-3. High frequencies of circulating CD14+CD204+ and CD14+CD163+CD204+ M2-like monocytes were associated with tumor-node-metastasis stage, lymph node metastasis, histological differentiation, and estrogen receptor expression. Circulating M2-like monocytes may serve as a diagnostic biomarker in breast cancer and have a potential role in reflecting breast cancer progression.