title: Flt-4-positive vessel density correlates with vascular endothelial growth factor-d expression, nodal status, and prognosis in breast cancer.
abstract: OBJECTIVE
  Metastasis to the regional lymph nodes through the lymphatic vessels is a common step in the progression of cancer and an important prognostic factor in many types of cancer. Recent evidence suggests that tumor lymphangiogenesis promotes lymphatic metastasis, and that the presence of Flt-4 on tumor blood and lymphatic vessels may play a important role in mediating lymphangiogenic factor-induced neovascularization. We assessed flt-4-positive vessel density (FVD) in breast cancer, and examined whether FVD associates with lymph node metastasis, VEGF-D expression, or prognosis.
  
  
  METHODS
  One hundred three invasive breast carcinomas with long-term follow-up were included in our study. Flt-4 was assessed using immunohistochemistry, then we analyzed the relationship between FVD and lymph node status, as well as VEGF-D expression and other established clinicopathological parameters. The relationship between FVD and prognosis was also investigated.
  
  
  RESULTS
  Mean FVD of "hot spot" was 29.3 +/- 22.5 for each case. FVD was correlated significantly with lymph node metastasis (P < 0.0001), VEGF-D expression (P = 0.0019), tumor size (P = 0.0015), estrogen receptor (P = 0.0211), progesterone receptor (P = 0.0462), and c-erbB-2 (P = 0.0326). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that high FVD was associated with both worse disease-free survival (P = 0.0035) and overall survival (P = 0.0336).
  
  
  CONCLUSIONS
  Increased FVD was correlated with lymph node metastasis and VEGF-D expression. High FVD may be a significant unfavorable prognostic factor for long-term survival in breast cancer. It is possible that Flt-4 becomes a target for antiangiogenic therapy to breast cancer.
authors: Second Department of Pathology, Wakayama Medical University, 641-8509 Wakayama City, Japan. ynakamur@mail.wakayama-med.ac.jp
authors: Yasushi
authors: Y
authors: Nakamura
authors: Hironao
authors: H
authors: Yasuoka
authors: Masahiko
authors: M
authors: Tsujimoto
authors: Qifeng
authors: Q
authors: Yang
authors: Shigeru
authors: S
authors: Imabun
authors: Masaaki
authors: M
authors: Nakahara
authors: Kazuyasu
authors: K
authors: Nakao
authors: Misa
authors: M
authors: Nakamura
authors: Ichiro
authors: I
authors: Mori
authors: Kennichi
authors: K
authors: Kakudo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3