Hypercholesterolemia impairs angiogenesis in patients with breast carcinoma and, therefore, lowers the risk of metastases

Am J Clin Pathol. 2004 Nov;122(5):696-703. doi: 10.1309/HW2M-YB5T-VF4A-M0Y4.

Abstract

Our aim was to study the effect of hypercholesterolemia on angiogenesis induced by breast carcinoma. Of 51 patients with invasive ductal carcinoma, 28 had hypercholesterolemia and 23 had normocholesterolemia. The intratumoral microvessel density (MVD) was evaluated by using anti-CD31 antibody. The expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on endothelial and tumor cells was examined and graded semiquantitatively. Patients with normocholesterolemia had a higher MVD (76.4 +/- 8.2) than those with hypercholesterolemia (54.6 +/- 5.1) (P < .01). The risks of recurrence and distant metastasis were higher in patients with normocholesterolemia than in patients with hypercholesterolemia (P < .01). Patients with hypercholesterolemia showed lower expression of endothelial VEGF and bFGF than patients with normocholesterolemia (P < .05 and P < .01, respectively). In addition, tumoral bFGF and VEGF expression showed negative correlation with the presence of hypercholesterolemia (P < .01). We suggest that hypercholesterolemia impairs angiogenesis by suppressing endothelial and tumoral bFGF and VEGF expression and, therefore, lowers the risk of metastases in cases of invasive breast carcinoma.

MeSH terms

  • Angiogenesis Inhibitors*
  • Breast Neoplasms / blood supply*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Female
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Hypercholesterolemia*
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology*
  • Neovascularization, Pathologic / pathology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Prognosis
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2