Stromal Infiltration of Tumor-Associated Macrophages Conferring Poor Prognosis of Patients with Basal-Like Breast Carcinoma

Mu Yang; Zhenhua Li; Meijing Ren; Shuai Li; Lanjing Zhang; Xinmin Zhang; Fangfang Liu

doi:10.7150/jca.25155

Stromal Infiltration of Tumor-Associated Macrophages Conferring Poor Prognosis of Patients with Basal-Like Breast Carcinoma

J Cancer. 2018 Jun 6;9(13):2308-2316. doi: 10.7150/jca.25155. eCollection 2018.

Authors

Mu Yang^{1

2}, Zhenhua Li¹, Meijing Ren¹, Shuai Li¹, Lanjing Zhang^{2

3

4

5}, Xinmin Zhang⁶, Fangfang Liu¹

Affiliations

¹ Department of Breast Pathology and Research Laboratory, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
² Department of Pathology, University Medical Center of Princeton, Plainsboro, NJ 08854, USA.
³ Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
⁴ Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA.
⁵ Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.
⁶ Department of Pathology, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, New Jersey 08103, USA.

Abstract

Aims: Tumor associated macrophages (TAMs) play a critical role in the initiation and progression of breast cancer. However, their prognostic significance in the molecular subtype of basal-like breast cancer (BLBC) is poorly understood. The aim of this study was to investigate the extent and patterns of TAMs in BLBC and their associations with clinicopathological features and patient survival. Methods and Results: We evaluated TAMs in 200 cases of BLBC by immunohistochemistry using the M2 macrophage marker CD163 and the pan-macrophage marker CD68 in tumor nest and stroma, and assessed their prognostic significance. The study demonstrated that infiltration of CD163⁺ and CD68⁺ macrophages in tumor stroma was of clinical relevance in BLBC, but not those in tumor nest. Increased stromal infiltration of CD68⁺ or CD163⁺ macrophages correlated with larger tumor size, higher histological grade, higher 5-year recurrence and 5-year breast cancer mortality. Although both of CD68⁺ and CD163⁺ macrophages in tumor stroma were associated with poor recurrence-free survival (RFS) and overall survival (OS), multivariate analysis demonstrated that only CD163⁺ macrophage was an independent predictor of RFS and OS. Conclusions: Our results highlight the prognostic importance of TAMs' location in BLBC. CD163, a highly specific biomarker for M2 macrophages, is an independent prognostic marker for BLBC patients, and may serve as an indicator or potential target of macrophage-centred therapeutic strategies.

Keywords: Basal-like breast cancer; CD163; CD68; Prognosis; Tumor associated macrophages.