title: Association between VEGF-A, C and D expression and lymph node involvement in breast cancer: a meta-analysis.
abstract: BACKGROUND
  Metastasis is the primary cause of death in patients with breast cancer. Although VEGF-A, C and D are considered to be prime factors in lymph node metastasis in breast cancer, the published studies have conflicting conclusions.
  
  
  METHODS
  To resolve this conflict, we conducted a meta-analysis of 37 studies (n = 5,001 patients) evaluating the correlation between VEGF-A, C and D immunohistochemical expression and lymph node metastasis (LNM). The meta-analysis included 22 studies of VEGF-A, 17 of VEGF-C, and 6 of VEGF-D. The relationships between VEGF-A, C and D and clinicopathological parameters were also examined.
  
  
  RESULTS
  The results showed a significant association between VEGF-A or VEGF-C overexpression and LNM (risk ratio [RR] = 1.28 [95% CI 1.04-1.58], p = 0.02; and RR = 1.36 [95% CI 1.07-1.72], p = 0.01, respectively). Subgroup evaluation showed a significant association between VEGF-A, C and D overexpression and LNM when analyses were limited to Asian patients (RR = 1.78 [95% CI 1.28-2.46], p = 0.0005; RR = 1.38 [95% CI 1.04-1.84], p = 0.03, and RR = 2.62 [95% CI 1.35-5.09], p = 0.004, respectively). VEGF-A overexpression was significantly associated with lymph vessel invasion (RR = 1.86 [95% CI 1.33-2.60], p = 0.0003). Overexpression of VEGF-C or VEGF-D was significantly associated with HER-2 positivity (RR = 1.30 [95% CI 1.06-1.59], p = 0.01; and RR = 1.75 [95% CI 1.01-3.03], p = 0.05, respectively).
  
  
  CONCLUSIONS
  With some limitations, our meta-analysis indicated that VEGF-A and C could predict LNM in patients with breast cancer, particularly Asian patients.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin - China.
authors.forename: Fei
authors.initials: F
authors.lastname: Su
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin - China.
authors.forename: Baoquan
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin - China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin - China.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin - China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin - China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin - China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin - China.
authors.forename: Kai
authors.initials: K
authors.lastname: You
authors.affiliation: Department of General Surgery, The Second Clinical Hospital, Harbin Medical University, Harbin - China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin - China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology*; D008207:Lymphatic Metastasis; D020033:Protein Isoforms; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis*
chemical_list: D020033:Protein Isoforms; D042442:Vascular Endothelial Growth Factors