Combined high expression of CD47 and CD68 is a novel prognostic factor for breast cancer patients

BACKGROUND: Avoiding the phagocytosis by tumor-associated macrophages (TAMs) is necessary for the growth and metastasis of solid tumors. CD47 binds to the receptor signal-regulatory protein-α (SIRP-α) on the macrophages to avoid normal phagocytosis. In this study, we evaluated the expression and prognostic significance of CD47 and CD68-labeled TAMs in breast cancer solid tumors. METHODS: Two hundred seventeen cases of breast cancer tissues and 40 cases of benign breast lesions were collected for immunohistochemical staining of CD47 and CD68. RESULTS: Both of the CD47 and CD68 expression were significantly higher in breast cancer tissues (P < 0.001), and associated with multiple clinicopathological parameters in breast cancer (P < 0.05). However, CD47 or CD68 expression alone was not an independent predictor of poor DFS in multivariate survival analysis (P > 0.05). Interestingly, combined high expression of CD47 and CD68 (CD47(high)CD68(high)) not only had a significant association with advanced TNM stage, histological grade, LNM, ER status, PR status and recurrence (P < 0.05), but also displayed a poorer 5-DFS (P = 0.011). Strikingly, CD47(high)CD68(high) served as a novel independent prognostic factor for poor DFS compared to the expression of CD47 or CD68 alone (P = 0.045). Furthermore, our study also showed for the first time that the prognostic significance of CD47(high)CD68(high) not only in breast cancer in general, but also in hormone receptor-negative breast cancer in particular. CONCLUSIONS: Combined detection of CD47 and CD68 may provide guidance for the prognosis of breast cancer, especially hormone receptor-negative breast cancer.