Tumor Angiogenesis in Breast Cancer: Pericytes and Maturation Does Not Correlate With Lymph Node Metastasis and Molecular Subtypes

Clin Breast Cancer. 2016 Apr;16(2):131-8. doi: 10.1016/j.clbc.2015.09.002. Epub 2015 Sep 25.

Abstract

Background: Angiogenesis, traditionally assessed by microvessel density (MVD), does not give an indication of the functional status of the tumor neovasculature. The structural and functional stability of the tumor vasculature and its potential clinical relevance in breast cancer was evaluated.

Materials and methods: In invasive breast cancer, immunostaining of endothelial cells and pericytes was performed using anti-CD34 and anti-platelet-derived growth factor receptor-β antibody, respectively. Double immunostaining for the proliferating capillary index (PCI) and microvessel pericyte coverage index (MPI) was performed with CD34/Ki-67 and CD34/smooth muscle actin.

Results: The mean MVD of 145 vessels/mm(2) was significantly greater in grade 3 tumors (P = .018) and in necrotic tumors (P = .022). The PCI ranged from 0% to 17.14% (mean, 4.37%) and was associated with a high proliferative index in tumor tissue (P = .044). The MPI ranged from 13.09% to 88.18% (mean, 41.35%), indicating the stability of the tumor vasculature. However, it was not significantly associated with the tumor size, tumor grade, lymph node metastasis, proliferative index, or molecular subtypes.

Conclusion: MVD remains the angiogenesis-related parameter associated with tumor grade and necrosis. The PCI was the only functional parameter of angiogenesis associated with a poor prognostic indicator. The MPI did not show any correlation with the known prognostic and predictive factors.

Keywords: Angiogenesis; Breast cancer; Microvessel density; Microvessel pericyte coverage; Proliferating capillary index.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / blood supply
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / secondary*
  • Carcinoma, Lobular / blood supply
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / secondary*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Pericytes / metabolism
  • Pericytes / pathology*
  • Prognosis
  • Prospective Studies
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2