VEGF-D in association with VEGFR-3 promotes nodal metastasis in human invasive lobular breast cancer

Am J Clin Pathol. 2007 Nov;128(5):759-66. doi: 10.1309/7FXVRMXF58PVRJUH.

Abstract

We assessed the expression of vascular endothelial growth factors (VEGF-C and VEGF-D) in breast cancer cells and the density of lymph vessels and VEGF receptor-3 (VEGFR-3)-positive vessels in and around the tumor in invasive lobular breast cancer. We found significant correlation between peritumoral lymph vessel density and presence of lymph node metastases (P=.001) and the number of metastatic lymph nodes (P<.001). A significant correlation was detected between tumor cell VEGF-D expression and lymph node status (P=.001) and density of lymphatic vessel endothelial receptor (LYVE)-1-positive vessels (P=.035). VEGFR-3+/VEGF-D+ and VEGFR-3+/VEGF-C+ tumors had a significantly higher number of metastatic lymph nodes than tumors with other staining patterns (P<.001). Tumors positive for neither VEGF-D nor VEGFR-3 had a lower density of LYVE-1+ vessels than tumors with other staining patterns (P=.033). Our results indicate that peritumoral lymph vessel density is associated with lymph node metastases in invasive lobular breast cancer and that invasive lobular cancer producing VEGF-D, surrounded by VEGFR-3+ vessels, has a significantly higher peritumoral lymph vessel density and a higher number of metastatic lymph nodes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Lobular / blood supply
  • Carcinoma, Lobular / metabolism*
  • Carcinoma, Lobular / secondary
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Vascular Endothelial Growth Factor D / metabolism*
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism*

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Vascular Endothelial Growth Factor D
  • Vascular Endothelial Growth Factor Receptor-3