title: Macrophage-colony stimulating factor (CSF1) predicts breast cancer progression and mortality.
abstract: BACKGROUND
  Macrophage colony-stimulating factor (CSF1), also known as colony-stimulating factor-1 (CSF1), and its receptor CSF1R have been correlated with poor prognosis in many cancer types including breast cancer. Herein, we investigated the prognostic impact of CSF1 and CSF1R expression in tumor epithelial and stromal compartments in primary breast cancer and axillary lymph node metastases. In addition, the density of CD68+ tumor-associated macrophages (TAMs) and CD3+ T-lymphocytes was examined.
  
  
  METHODS
  Tumor tissue was obtained at the time of primary surgery from 68 prior treatment breast cancer patients, 38 with axillary lymph node metastases and 30 patients without metastases. Digital video analysis was performed on immunohistochemically stained slides.
  
  
  RESULTS
  The expression of CSF1, CSF1R and the density of TAMs and CD3+ T-lymphocytes were then correlated to metastases and disease-specific mortality. Metastasized primary cancers had higher tumor epithelial and stromal expressions of CSF1 (p<0.001 and p=0.002, respectively) and CSF1R (both p=0.03) compared to non-metastatic cancers. Similar findings were made for the density of CD68+ (p=0.003) and CD3+ cells in the tumor epithelium (p<0.001). In multivariate analysis, a high tumor epithelial expression of CSF1 in primary breast cancer predicted mortality (hazard ratio (HR)=8.6, p=0.039).
  
  
  CONCLUSIONS
  High expression of CSF1 and CSF1R and high density of TAMs and CD3+ T-lymphocytes were related to breast cancer progression. CSF1 expression in tumor epithelium predicted breast cancer mortality.
authors: Department of Clinical Pathology, University Hospital of Northern Norway, Tromsø, Norway Department of Medical Biology, The Arctic University of Norway, Tromsø, Norway elin.richardsen@unn.no.
authors: Elin
authors: E
authors: Richardsen
authors: Department of Clinical Pathology, University Hospital of Northern Norway, Tromsø, Norway.
authors: Rebecca Dale
authors: RD
authors: Uglehus
authors: Department of Neurology and Clinical Neurophysiology, University Hospital of Northern Norway, Tromsø, Norway Department of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway.
authors: Stein Harald
authors: SH
authors: Johnsen
authors: Department of Clinical Pathology, University Hospital of Northern Norway, Tromsø, Norway Department of Medical Biology, The Arctic University of Norway, Tromsø, Norway.
authors: Lill-Tove
authors: LT
authors: Busund
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D016173:Macrophage Colony-Stimulating Factor
keywords: Breast cancer; CSF1; CSF1R; T-lymphocytes; epithelial tumor cells; metastases; tumor stromal cells; tumor-infiltrating macrophages