title: Expression of angiopoietin-2 and vascular endothelial growth factor receptor-3 correlates with lymphangiogenesis and angiogenesis and affects survival of oral squamous cell carcinoma.
abstract: BACKGROUND
  Both Ang-2 and VEGFR-3 are major regulators of angiogenesis and lymphangiogenesis, respectively, and thus may affect prognosis of OSCC. We sought to determine the associations between Ang-2 and VEGFR-3 expression and survival of OSCC.
  
  
  METHODS
  Ang-2 and VEGFR-3 expression was determined immunohistochemically in tumor tissues from 112 patients with OSCC; OSCC-adjacent noncancerous oral tissue from 85 OSCC patients; and normal oral mucosa from 37 cancer-free individuals. A log-rank test and Cox proportional hazard models were used to compare survival among different groups with expression of Ang-2 and VEGFR-3.
  
  
  RESULTS
  Ang-2 and VEGFR-3 expression was upregulated in OSCC compared to nontumor tissue (all P<0.05). High Ang-2 expression positively correlated with microvessel density (MVD) (P<0.01), and high VEGFR-3 expression positively correlated with lymph node metastasis (P<0.01) and lymphatic vessel density (LVD) (P<0.01). The patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly worse survival than in patients with low expression of Ang-2 or any other co-expression status (all P<0.05), respectively. Furthermore, multivariable analysis showed that patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly increased risk of death compared with those with low expression of Ang-2 or any other co-expression status (HR, 2.7, 95% CI, 1.1-6.2 and 5.0, 1.3-15.4, respectively).
  
  
  CONCLUSIONS
  These results suggest that increased expression in tumors of Ang-2 may individually, or in combination with VEGFR-3, predict poor prognosis of OSCC.
authors.affiliation: Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China ; State Key Laboratory of Oral Diseases in Sichuan University, Sichuan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Fan
authors.forename: Xicheng
authors.initials: X
authors.lastname: Song
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Chunhua
authors.initials: C
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Mi
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Song
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Tao
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000503:physiopathology; D008297:Male; D055806:Microvessels / Q000503:physiopathology; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D009389:Neovascularization, Pathologic; D016019:Survival Analysis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
chemical_list: D042702:Angiopoietin-2; D040321:Vascular Endothelial Growth Factor Receptor-3
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