title: Combination of low vascular endothelial growth factor A (VEGF-A)/VEGF receptor 2 expression and high lymphocyte infiltration is a strong and independent favorable prognostic factor in patients with nonsmall cell lung cancer.
abstract: BACKGROUND
  There seems to be a close interplay between angiogenesis and the immune system. The authors of this report investigated the prognostic role of angiogenic markers in coexpression with immune system markers in patients with nonsmall cell lung cancer (NSCLC).
  
  
  METHODS
  Tumor resection samples from 335 patients with stage I to IIIA NSCLC were obtained, and tissue microarrays were constructed. Immunohistochemistry was used to evaluate the expression of vascular endothelial growth factor (VEGF) A (VEGF-A), VEGF receptor 2 (VEGFR-2), and lymphocytes that were positive for the cluster of differentiation 4 (CD4) and CD8 coreceptors.
  
  
  RESULTS
  In univariate analysis, 5-year survival rates were 87% for the combination of low tumor cell expression of VEGF-A and VEGFR-2 (↓VEGF-A/↓VEGFR-2) and high tumor cell expression of CD4 and CD8 (↑CD4/↑CD8) (n = 19), 58% for mixed combinations (n = 290), and 27% for the ↑VEGF-A/↑VEGFR-2 and ↓CD4/↓CD8 combination (n = 26). In multivariate analysis, the coexpression of ↑VEGF-A/↑VEGFR-2 and ↓CD4/↓CD8 was an independent negative prognostic factor (hazard ratio, 9.16; 95% confidence interval, 2.11-39.8; P = .003).
  
  
  CONCLUSIONS
  Low tumor cell VEGF-A and VEGFR-2 expression in combination with high adaptive immune cell expression in the tumor-related stroma had a strong and independent favorable prognostic impact in patients with NSCLC.
authors.affiliation: Institute of Clinical Medicine, University of Tromso, Tromso, Norway. tom.donnem@uit.no
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Shibli
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000369:Aged, 80 and over; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2