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Tumour-infiltrating macrophages and clinical outcome in breast cancer
  1. S M A Mahmoud1,2,
  2. A H S Lee3,
  3. E C Paish3,
  4. R D Macmillan4,
  5. I O Ellis1,3,
  6. A R Green1
  1. 1Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, UK
  2. 2Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
  3. 3Department of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham, UK
  4. 4The Breast Institute, Nottingham University Hospitals NHS Trust, Nottingham, UK
  1. Correspondence to Dr Andrew R Green, Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK;{at}


Background Macrophages constitute a major component of the leucocytic infiltrate of tumours. Human studies show an association between tumour-associated macrophages and tumours with poor prognostic features. In breast cancer, the presence of macrophages has been correlated with increased angiogenesis and poor prognosis but little information is available about the independent prognostic role of macrophages infiltrating breast carcinomas.

Aims and methods This study used immunohistochemistry and tissue microarrays to assess the density and localisation of CD68 macrophages infiltrating 1322 breast tumours and to identify any relationship with clinicopathological factors and patient outcome.

Results Tumour-infiltrating macrophages were present in the majority of tumours with a predominantly diffuse pattern. The density of distant stromal macrophages (infiltrating stroma away from the carcinoma, median count 14 cells) was higher than intratumoural (median zero cells) and adjacent stromal macrophages (median three cells). Higher total macrophage number was associated with higher tumour grade (rs=0.39, p<0.001), ER and PgR negativity, HER-2 positivity and basal phenotype (p<0.001). In univariate survival analysis, higher numbers of CD68 macrophages were significantly associated with worse breast cancer-specific survival (p<0.001) and shorter disease-free interval (p=0.004). However in multivariate model analysis, the CD68 macrophage count was not an independent prognostic marker.

Conclusions Macrophages are heterogeneous with different subsets having different functions. The present study suggests that overall macrophage numbers are not related to prognosis in breast cancer. However, further studies are needed to investigate the potential role of different subsets of macrophages.

  • Angiogenesis
  • breast
  • breast cancer
  • breast pathology
  • cancer
  • CD68
  • cytology
  • diagnosis
  • endocrinology
  • histopathology
  • immunocytochemistry
  • immunohistochemistry
  • immunology
  • molecular biology
  • molecular oncology
  • molecular pathology
  • panmacrophage
  • PCR
  • steroid receptors
  • tamoxifen
  • tumour angiogenesis
  • tumour-associated macrophages

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  • Competing interests None.

  • Ethics approval Ethics approval was provided by Nottingham Research Ethics Committee 2 under the title of development of a molecular genetic classification of breast cancer.

  • Provenance and peer review Not commissioned; externally peer reviewed.