J Cancer 2019; 10(19):4463-4472. doi:10.7150/jca.33914 This issue

Research Paper

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

Chao Ni1,2✉, Liu Yang2, Qiuran Xu2, Hongjun Yuan3, Wei Wang4, Wenjie Xia3, Dihe Gong5, Wei Zhang6, Kun Yu3✉

1. Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second affiliated hospital, Zhejiang University, Hangzhou, Zhejiang, 310009
2. Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province
3. Department of Breast Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310003, China
4. Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310003, China
5. Department of Thyroid and Breast Surgery, Affiliated Cixi Hospital, Wenzhou Medical University, Cixi Zhejiang 315300, China
6. Department of Endocrinology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310003, China

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Citation:
Ni C, Yang L, Xu Q, Yuan H, Wang W, Xia W, Gong D, Zhang W, Yu K. CD68- and CD163-positive tumor infiltrating macrophages in non-metastatic breast cancer: a retrospective study and meta-analysis. J Cancer 2019; 10(19):4463-4472. doi:10.7150/jca.33914. Available from https://www.jcancer.org/v10p4463.htm

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Abstract

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.

Keywords: breast cancer, macrophage, CD68, CD163