title: The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.
abstract: BACKGROUND
  We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM) expression of proteins associated with M1 and M2 macrophages in NSCLC.
  
  
  METHODS
  Using immunohistochemistry, CD68(+) macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14), or a non-cytotoxic M2 phenotype (CD163 and VEGF) were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES) (median 92.7 months) and 20 patients with poor survival (PS) (median 7.7 months).
  
  
  RESULTS
  The NM expression of NM-HLA-DR (p<0.001), NM-iNOS (p = 0.02) and NM-MRP 8/14 (p = 0.02) was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001). There was more NM-CD163 expression (p = 0.04) but less NM-iNOS (p = 0.002) and MRP 8/14 (p = 0.01) expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001), 65.0% versus 14.6% (NM-iNOS p = 0.003), and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04), as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41) and 19.4% versus 59.0% (NM-VEGF p = 0.001).
  
  
  CONCLUSIONS
  Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom. cohri@doctors.org.uk
authors.forename: Chandra M
authors.initials: CM
authors.lastname: Ohri
authors.forename: Aarti
authors.initials: A
authors.lastname: Shikotra
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Green
authors.forename: David A
authors.initials: DA
authors.lastname: Waller
authors.forename: Peter
authors.initials: P
authors.lastname: Bradding
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D040501:Calgranulin A / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011379:Prognosis; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism; D015203:Reproducibility of Results; D016019:Survival Analysis; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D040501:Calgranulin A; D040502:Calgranulin B; D006684:HLA-DR Antigens; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D052247:Nitric Oxide Synthase Type II