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

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Abstract

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.

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Funding

This study was supported by the SingHealth Foundation (SHF) Research Grant, SHF/FG668S/2015, awarded to Dr. Aye Aye Thike.

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Authors and Affiliations

  1. Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore

    Xiao-Yang Chen, Aye Aye Thike, Nur Diyana Md Nasir, Valerie Cui Yun Koh & Puay Hoon Tan

  2. Duke-NUS Medical School, Singapore, Singapore

    Xiao-Yang Chen, Aye Aye Thike & Puay Hoon Tan

  3. Division of Pathology, Singapore General Hospital, Singapore, Singapore

    Xiao-Yang Chen & Puay Hoon Tan

  4. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Xiao-Yang Chen, Boon Huat Bay & Puay Hoon Tan

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  1. Xiao-Yang Chen
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Contributions

AT conceived and directed the study. AT, PT and BB supervised the research. VK prepared tissue sections, performed IHC and collated data. AT and NM performed immunohistochemical scoring. AT and XC interpreted data and performed biostatistical analysis. PT and BB contributed to the scientific content of the study. XC drafted the manuscript with the assistance and final approval of all authors.

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Correspondence to Puay Hoon Tan.

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This study was approved by The SingHealth Centralized Institutional Review Board (CIRB), Ref No. 2016/2393.

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The authors declare that they have no conflict of interest.

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Chen, XY., Thike, A.A., Md Nasir, N.D. et al. Higher density of stromal M2 macrophages in breast ductal carcinoma in situ predicts recurrence. Virchows Arch 476, 825–833 (2020). https://doi.org/10.1007/s00428-019-02735-1

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