title: Clinical significance of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma.
abstract: BACKGROUND
  Vascular endothelial growth factor-C (VEGF-C) plays an important role in lymphangiogenesis and activates VEGF receptor-3 (VEGFR-3). Lymphatic spread is an important prognostic factor in patients with lung adenocarcinoma. The aim of the current study was to determine whether the expression of VEGF-C and VEGFR-3 correlates with clinicopathologic factors and prognosis in patients with TNM classification T1 lung adenocarcinoma.
  
  
  METHODS
  The authors conducted a retrospective review of 129 consecutive patients who underwent complete resection for T1 lung adenocarcinoma. Immunohistochemical staining for VEGF-C, VEGF, VEGFR-3, CD34 (microvessels), tryptase (mast cells), and CD68 (macrophages) was performed to statistically analyze clinicopathologic implications of VEGF-C and VEGFR-3 status.
  
  
  RESULTS
  Of 129 patients with T1 lung adenocarcinoma, 56 (43.3%) patients were positive for tumor-cell VEGF-C and 73 (56.6%) and 69 (53.5%) patients were positive for tumor-cell and endothelial-cell VEGFR-3, respectively. Patients with positive staining for tumor-cell VEGF-C showed significantly less favorable survival rates than patients with negative staining (P = 0.031). The survival rates of patients with positive staining for tumor-cell and endothelial-cell VEGFR-3 were significantly lower than those with negative staining (P = 0.0034 and P = 0.0020, respectively). Patients with positive staining for both tumor-cell VEGF-C and endothelial-cell VEGFR-3 exhibited the most unfavorable prognoses. Multivariate analysis demonstrated that coexpression of tumor-cell VEGF-C and endothelial-cell VEGFR-3 was an independent negative prognostic factor (P = 0.0129) as well as N factor (P = 0.0020).
  
  
  CONCLUSIONS
  VEGF-C and VEGFR-3 status may be indicative of survival rates for patients with T1 lung adenocarcinoma.
authors.affiliation: Department of Respiratory Medicine, Obihiro Kyokai Hospital, Obihiro, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kojima
authors.forename: Noriharu
authors.initials: N
authors.lastname: Shijubo
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
authors.forename: Shingo
authors.initials: S
authors.lastname: Ichimiya
authors.forename: Shosaku
authors.initials: S
authors.lastname: Abe
authors.forename: Masaaki
authors.initials: M
authors.lastname: Satoh
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012697:Serine Endopeptidases / Q000378:metabolism; D015996:Survival Rate; D053802:Tryptases; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3; D012697:Serine Endopeptidases; D053802:Tryptases