Higher density of stromal M2 macrophages in breast ductal carcinoma in situ predicts recurrence

Immune response can affect tumour progression and treatment outcome. This study investigated the potential of stromal macrophages around ductal carcinoma in situ (DCIS) in predicting recurrence and progression. CD68 and CD163 expression of macrophages in DCIS from 198 patients was determined by immunohistochemistry. Disease free survival (DFS), clinicopathological parameters and biomarker expression were correlated with the densities of both CD68(+) and CD163(+) macrophages. High CD68(+) macrophage density was associated with high nuclear grade (p < 0.001), oestrogen receptor (ER) negativity (p = 0.029), progesterone receptor (PR) negativity (p = 0.008) and human epidermal growth factor receptor 2 (HER2) positivity (p < 0.001). High CD163(+) macrophage density was associated with high nuclear grade (p = 0.003), microinvasion (p = 0.01), ER negativity (p < 0.001), PR negativity (p = 0.001), HER2 positivity (p = 0.001) and triple negativity (p = 0.022). DCIS with higher CD68(+) macrophage density disclosed significantly worse DFS for ipsilateral invasive recurrence (p = 0.004) and is affirmed by multivariate Cox regression analysis (95% CI 1.126-5.102, HR = 2.397, p = 0.023). DCIS with higher CD163(+) macrophage density showed significantly worse DFS for both recurrence (p = 0.001) and ipsilateral invasive recurrence (p = 0.001). These findings, for CD163(+) macrophage density, were affirmed by multivariate Cox regression analysis respectively for both recurrence (95% CI 1.210-2.293, HR = 1.880, p = 0.005) and ipsilateral invasive recurrence (95% CI 1.122-5.176, HR = 2.410, p = 0.024). This study demonstrated that DCIS with higher macrophage density was associated with poorer prognostic parameters, while DCIS with higher CD163(+) macrophage density predicted both recurrence and ipsilateral invasive recurrence.