title: Lymphangiogenic Markers and Their Impact on Nodal Metastasis and Survival in Non-Small Cell Lung Cancer--A Structured Review with Meta-Analysis.
abstract: BACKGROUND
  In non-small cell lung cancer (NSCLC), nodal metastasis is an adverse prognostic factor. Several mediating factors have been implied in the development of nodal metastases and investigated for predictive and prognostic properties in NSCLC. However, study results differ. In this structured review and meta-analysis we explore the published literature on commonly recognized pathways for molecular regulation of lymphatic metastasis in NSCLC.
  
  
  METHODS
  A structured PubMed search was conducted for papers reporting on the expression of known markers of lymhangiogenesis in NSCLC patients. Papers of sufficient quality, presenting survival and/or correlation data were included.
  
  
  RESULTS
  High levels of vascular endothelial growth factor C (VEGF-C, HR 1.57 95% CI 1.34-1.84) and high lymphatic vascular density (LVD, HR 1.84 95% CI 1.18-2.87) were significant prognostic markers of poor survival and high expression of VEGF-C, vascular endothelial growth factor receptor 3 (VEGFR3) and LVD was associated with lymph node metastasis in NSCLC.
  
  
  CONCLUSIONS
  Lymphangiogenic markers are prognosticators of survival and correlate with lymph node metastasis in NSCLC. Their exact role and clinical implications should be further elucidated.
authors: Department of Oncology, University Hospital of North Norway, Tromso, Norway; Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors: Thomas K
authors: TK
authors: Kilvaer
authors: Department of Oncology, University Hospital of North Norway, Tromso, Norway; Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors: Erna-Elise
authors: EE
authors: Paulsen
authors: Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors: Sigurd M
authors: SM
authors: Hald
authors: Department of Community Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors: Tom
authors: T
authors: Wilsgaard
authors: Department of Oncology, University Hospital of North Norway, Tromso, Norway; Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors: Roy M
authors: RM
authors: Bremnes
authors: Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway; Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
authors: Lill-Tove
authors: LT
authors: Busund
authors: Department of Oncology, University Hospital of North Norway, Tromso, Norway; Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors: Tom
authors: T
authors: Donnem
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology*; D017594:Publication Bias; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor