title: Loss of Nm23 is associated with a more favorable tumor microenvironment in patients with breast cancer.
abstract: Nm23 is a metastasis suppressor gene whose downregulation triggers metastatic progression. The aim of this study was to investigate the expression of Nm23 in breast carcinomas and its relationship with tumor microenvironment markers.
  
  
  
  A retrospective study was done (128 breast cancer patients from 2007 to 2010). Nm23, LPA1, SMA, CD34, CD8, and CD68 protein expressions were evaluated using immunohistochemistry. Image analysis was used to determine the immunostaining percentage area of Nm23, LPA1, and SMA; the number of the total vessel fraction CD34 positive; and the number of CD8+ and CD68+ cells. The mean ± SE was calculated. The differences among groups were evaluated using Student t-test for parametric data and Mann Whitney U test for nonparametric data.
  
  
  
  Cases were divided into two groups: Nm23+ and Nm23-. LPA1 immunostaining was significantly increased in Nm23- group. Immunostaining percentage area of SMA was not significantly higher when Nm23 was negative. CD34 immunopositive blood vessels, number of T CD8+ cells, and the number of macrophage CD68+ cells were increased when Nm23 was absent.
  
  
  
  Our results suggest that the absence of Nm23 causes an increase in LPA1, CD8+ and CD68+ inflammatory cells, and angiogenesis marker. Therefore, Nm23 loss could be associated with a more favorable environment for the development and dissemination of breast cancer. However, more studies are needed to determine this association.
authors.affiliation: Histology Laboratory, Institute of Applied Molecular Medicine, Department of Basic Medical Sciences, School of Medicine, CEU-San Pablo University, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Durán
authors.affiliation: Department of Quantitative Methods, School of Pharmacy, CEU-San Pablo University, Madrid, Spain.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Cárdenas
authors.affiliation: Department of Anesthesiology, Madrid-Montepríncipe University Hospital, Madrid, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Reina
authors.affiliation: Histology Laboratory, Institute of Applied Molecular Medicine, Department of Basic Medical Sciences, School of Medicine, CEU-San Pablo University, Madrid, Spain. arriazun@ceu.es.
authors.forename: Riánsares
authors.initials: R
authors.lastname: Arriazu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes; D004777:Environment; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018655:Lymphocyte Count; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000473:pathology; D012189:Retrospective Studies; D059016:Tumor Microenvironment; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C517938:NME1 protein, human