title: Macrophage colony-stimulating factor-1 receptor expression is associated with poor outcome in breast cancer by large cohort tissue microarray analysis.
abstract: OBJECTIVE
  Macrophage colony-stimulating factor-1 receptor (CSF-1R) is a transmembrane tyrosine kinase receptor, which is abnormally expressed in invasive breast cancer. Small cohort studies have demonstrated that increased expression of CSF-1R is associated with ipsilateral breast cancer recurrence. Correlation with survival has not been reported. Our aim was to further evaluate the role of CSF-1R in breast cancer, by studying the expression of CSF-1R in a large cohort of clinical specimens.
  
  
  METHODS
  Tissue microarrays containing 301 node-negative and 280 node-positive cases were used. Immunohistochemical staining was performed and correlated with overall survival, nodal status, and other clinicopathological data.
  
  
  RESULTS
  CSF-1R expression was strongly associated with nodal status. Of the node-negative cases, 114 (38.9%) stained positive for CSF-1R, whereas 189 (67.5%) of the node-positive cases expressed CSF-1R (P < 0.0001). CSF-1R expression is also associated with larger tumor size (P = 0.02). Positive staining was strongly associated with decreased survival (P = 0.0003). Among node-negative patients, CSF-1R expression was associated with decreased overall survival (P = 0.045), whereas among node-positive patients, it was not (P = 0.47). In multivariate analysis, CSF-1R was not independent of nodal status as a predictor of survival.
  
  
  CONCLUSIONS
  CSF-1R expression is a strong predictor of poor outcome in nonmetastatic breast cancer. It is significantly more frequently expressed in patients with nodal involvement. Among the node-negative patients, it has a stronger association with survival than among the node-positive patients. Our findings support other preclinical findings that CSF-1R may be involved in local invasion and metastasis. Thus, this receptor may be an effective target for therapeutic agents.
authors.affiliation: Departments of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. Harriet.Kluger@Yale.edu
authors.forename: Harriet M
authors.initials: HM
authors.lastname: Kluger
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolled-Filhart
authors.forename: Sofya
authors.initials: S
authors.lastname: Rodov
authors.forename: Barry M
authors.initials: BM
authors.lastname: Kacinski
authors.forename: Robert L
authors.initials: RL
authors.lastname: Camp
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D016186:Receptor, Macrophage Colony-Stimulating Factor