Tumor-associated macrophages and crown-like structures in adipose tissue in breast cancer

Purpose: We aimed to evaluate macrophage infiltration and to identify the status of crown-like structures (CLSs) in mammary adipose tissue of human breast tissue in cases with and without breast cancer. Methods: Breast adipose tissue was obtained from reduction mammoplasty (N = 56, Group 1), non-neoplastic breast tissue of breast cancer patients (N = 84, Group 2), and breast cancer with adipose stroma (N = 140, Group 3). Immunohistochemical staining of CD68 and CD163 was performed, and the infiltrating macrophages and CLSs within breast adipose tissue were evaluated. Results: Group 3 had the largest number of CD68-positive (CD68 ⁺ ) and CD163-positive (CD163 ⁺ ) macrophages and CLSs within adipose tissue (P < 0.001). Among Group 3, cases with high levels of CD68 ⁺ and CD163 ⁺ macrophages commonly had a higher histologic grade (P = 0.016 and P = 0.045), and cases with CD163 ⁺ CLSs were correlated with old age (P = 0.042), estrogen receptor negativity (P = 0.013), human epidermal growth factor receptor-2 positivity (P = 0.043), and non-luminal A type (P = 0.039). Upon univariate analysis, high levels of CD163 ⁺ macrophages were associated with shorter disease-free survival in node-negative breast cancer patients (P = 0.033), and CD68 ⁺ CLSs were associated with shorter overall survival in node-positive breast cancer patients (P = 0.015). Conclusions: CD68 ⁺ and/or CD163 ⁺ tumor-associated macrophage infiltration as well as CLSs are present in adipose tissue nearby the breast cancer lesion, and are associated with various clinicopathologic parameters of breast cancer.