High LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer

Clin Cancer Res. 2004 Nov 1;10(21):7144-9. doi: 10.1158/1078-0432.CCR-03-0826.

Abstract

Purpose: 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.

Experimental design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / biosynthesis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Disease-Free Survival
  • Endothelium / metabolism*
  • Female
  • Glycoproteins / pharmacology*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Immunohistochemistry
  • Lymphatic Vessels / pathology*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis
  • Prognosis
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor C / biosynthesis
  • Vascular Endothelial Growth Factor Receptor-3 / biosynthesis
  • Vesicular Transport Proteins

Substances

  • Antigens, CD34
  • Glycoproteins
  • Hyaluronan Receptors
  • LYVE1 protein, human
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor C
  • Vesicular Transport Proteins
  • Vascular Endothelial Growth Factor Receptor-3