title: Prognostic significance of vascular endothelial growth factor D in breast carcinoma with long-term follow-up.
abstract: OBJECTIVE
  Expression of angiogenic and lymphangiogenic factors by tumors may influence the route of metastatic spread. The angiogenic factor vascular endothelial growth D (VEGF-D) is implicated in the development of lymphatic vessels and promotion of lymphatic metastases. The purpose of this study is to determine whether VEGF-D correlates with lymph node metastasis or prognosis.
  
  
  METHODS
  We assessed VEGF-D expression using immunohistochemistry in 105 invasive breast carcinomas with long-term follow-up. The relationship among VEGF-D expression, lymph node status, and other established clinicopathological parameters was assessed. Whether VEGF-D expression plays prognostic role in breast cancer was also investigated.
  
  
  RESULTS
  VEGF-D expression was identified in 86 cases (81.9%). Positive VEGF-D was significantly correlated with lymph node metastasis (P = 0.0238) and high c-erbB-2 expression (P = 0.0211). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that positive VEGF-D was associated with both disease-free survival (P = 0.0023) and overall survival (P = 0.0222). In multivariate analysis using the Cox regression model, positive emerged as an independent indicator for disease-free survival (P = 0.0452).
  
  
  CONCLUSIONS
  VEGF-D expression is associated with lymph node metastasis and may be a novel prognostic factor in breast cancer. VEGF-D may be useful in the treatment of breast cancer as a decision-making biomarker for aggressive treatment after operation.
authors.affiliation: Second Department of Pathology, Wakayama Medical University, 641-8509 Wakayama City, Japan. ynakamur@mail.wakayama-med.ac.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hironao
authors.initials: H
authors.lastname: Yasuoka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.forename: Shigeru
authors.initials: S
authors.lastname: Imabun
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakahara
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Nakao
authors.forename: Misa
authors.initials: M
authors.lastname: Nakamura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mori
authors.forename: Kennichi
authors.initials: K
authors.lastname: Kakudo
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D042643:Vascular Endothelial Growth Factor D
chemical_list: D016228:Endothelial Growth Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D042643:Vascular Endothelial Growth Factor D