title: VEGF-A and VEGFR-3 correlate with nodal status in operable non-small cell lung cancer: inverse correlation between expression in tumor and stromal cells.
abstract: BACKGROUND
  Lymph node metastasis is an essential determinant for stage and clinical management of non-small cell lung cancer (NSCLC). The vascular endothelial growth factors (VEGFs) and receptors (VEGFRs) are fundamental molecules in angiogenesis and lymphangiogenesis. We aimed to explore the correlations between nodal metastasis and the expression of VEGFs and VEGFRs in tumor cells and in tumor-related stroma.
  
  
  METHODS
  Tumor tissue samples from 335 resected patients with stage I-IIIA NSCLC were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and surrounding stromal tissue from each resected specimen. Immunohistochemistry was used to evaluate the expression of VEGF-A, VEGF-C, and VEGF-D and VEGFR-1, VEGFR-2 and VEGFR-3.
  
  
  RESULTS
  There were 232 N0 and 103 N+ patients (76 N1, 27 N2). In multivariate analyses, low stromal VEGF-A expression (P=0.018) is associated with N+ status. In tumor cells, strong correlations exist between high VEGF-A expression (P=0.032) and N+ status, and high VEGFR-3 expression (P<0.001) and N2-status.
  
  
  CONCLUSIONS
  The converse impact by stromal VEGF-A versus tumor cell VEGF-A expression on nodal metastasis may allude the importance of the tumor-stroma interaction when trying to understand lymphatic metastasis in NSCLC.
authors.affiliation: Department of Oncology, Institute of Clinical Medicine, University of Tromso, Tromso, Norway. tom.donnem@fagmed.uit.no
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Shibli
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.forename: Marit P
authors.initials: MP
authors.lastname: Delghandi
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017154:Stromal Cells / Q000737:chemistry; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040321:Vascular Endothelial Growth Factor Receptor-3