title: High LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer.
abstract: OBJECTIVE
  The clinical significance of intratumoral or peritumoral lymph vessel density is not known. LYVE-1, a lymphatic endothelium-specific hyaluronan receptor, is a novel lymphatic vessel marker that is expressed on lymph vessel endothelial cells of both normal and neoplastic tissues.
  
  
  METHODS
  We investigated expression of LYVE-1 by immunohistochemistry in 180 unilateral, invasive ductal breast carcinomas and assessed the presence and density of lymph vessels within the tumor and at the tumor periphery.
  
  
  RESULTS
  A minority (12%) of breast carcinomas had intratumoral lymph vessels, whereas peritumoral lymph vessels were identified in almost all cases (94%). No substantial association was found between the number of LYVE-1-positive vessels and the number of CD31 or vascular endothelial growth factor receptor-3-positive vessels, or vascular endothelial growth factor-C expression. The number of metastatic axillary lymph nodes increased in parallel with increasing lymph vessel counts (P = 0.033). A higher than the median lymph vessel count at the tumor periphery was significantly associated with unfavorable distant disease-free survival and overall survival. Women with high peritumoral lymph vessel density had only 58% (95% confidence interval, 46-70%) 5-year distant disease-free survival as compared with 74% (66-83%) among those with a low peritumoral lymph vessel density (P = 0.0088). In contrast, the presence of intratumoral lymph vessels was associated with neither axillary nodal status nor survival. Lymph vessel density was not an independent prognostic factor in a multivariate survival analysis.
  
  
  CONCLUSIONS
  A high peritumoral lymph vessel density is associated with a poor outcome in ductal breast cancer.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland. Petri.bono@hus.fi
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Wasenius
authors.forename: Päivi
authors.initials: P
authors.lastname: Heikkilä
authors.forename: Johan
authors.initials: J
authors.lastname: Lundin
authors.forename: David G
authors.initials: DG
authors.lastname: Jackson
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D004727:Endothelium / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D042601:Lymphatic Vessels / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis; D033921:Vesicular Transport Proteins
chemical_list: D018952:Antigens, CD34; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C119248:LYVE1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042582:Vascular Endothelial Growth Factor C; D033921:Vesicular Transport Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3