Elevated levels of tumour endothelial marker-8 in human breast cancer and its clinical significance

Int J Oncol. 2006 Nov;29(5):1311-7.

Abstract

Tumour endothelial marker-8 (TEM-8) belongs to a family of endothelial markers that are raised during tumour angiogenesis. We have recently reported aberrant expression of TEMs at the mRNA level in human breast cancer. This study sought to examine the level of TEM-8 expression at the protein and mRNA level in human breast cancer tissue, and in a panel of human breast cancer cell lines. We also wished to determine if TEM-8 can be used as a suitable marker for identifying tumour associated micro-vessels. At the mRNA level more tumours showed positive TEM-8 expression compared to normal background tissue. TEM-8 was detected in a variety of breast cancer cell lines, endothelial cells (HECV) and in a human fibroblast cell line (MRC5) at both the mRNA and protein level. Using immunohistochemistry the distribution of TEM-8 staining was more widespread in invasive breast cancer tissue compared to normal background tissue. Furthermore, the TEM-8 marker was found to be more discriminatory in identifying micro-vessels in tumour endothelium (2.8+/-0.83 vs. normal 1.66+/-0.52; P<0.011), compared to the vWFA marker (1.61+/-0.54 vs. normal 2.71+/-0.76; P<0.009). Raised levels of TEM-8 were associated with shorter survival outcome, but were not correlated to disease-free survival as shown by Kaplan-Meier and Cox regression analysis. We conclude that TEM-8 is a useful marker for identifying tumour associated micro-vessels and that elevated levels are associated with disease progression, which may have some bearing on the prognostic outcome in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Breast Neoplasms / blood supply*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / pathology
  • Capillaries / pathology
  • Cell Line, Tumor
  • Humans
  • Immunohistochemistry
  • Membrane Proteins / analysis*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microfilament Proteins
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neovascularization, Pathologic / diagnosis*
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / analysis*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • ANTXR1 protein, human
  • Biomarkers, Tumor
  • Membrane Proteins
  • Microfilament Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, Cell Surface