Low microvascular density at the tumor center is related to the expression of metalloproteases and their inhibitors and with the occurrence of distant metastasis in breast carcinomas

Int J Clin Oncol. 2013 Aug;18(4):629-40. doi: 10.1007/s10147-012-0428-2. Epub 2012 Jun 12.

Abstract

Background: The aims of this study were to evaluate the microvascular density (MVD) at the center of breast carcinomas, its relationship with the expression of metalloproteases (MMPs) and their inhibitors (TIMPs), and its connection with the distant metastasis rate.

Methods: An immunohistochemical study of four MMPs and two TIMPs was performed on cancer specimens from 97 women with a histological confirmed diagnosis of early invasive breast cancer.

Results: Expressions of MMP-9 by cancerous cells, or MMP-11 and TIMP-2 by stromal cells, were all negative and significantly associated with MVD, whereas MMP-7 score values were positive and also significantly associated with MVD. However, positive expression of MMP-1 by mononuclear inflammatory cells was significantly associated with MVD. Multivariate analysis demonstrated a significant and inverse relationship between MVD and the occurrence of distant metastasis.

Conclusions: Our data point out the clinical importance of low MVD at the tumor center as an independent prognostic factor of distant metastasis development in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / blood supply*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / blood supply*
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology*
  • Female
  • Humans
  • Matrix Metalloproteinase 11 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Metalloproteases / metabolism*
  • Microvessels / metabolism
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prognosis
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Tissue Inhibitor of Metalloproteinases / metabolism*

Substances

  • Biomarkers, Tumor
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinases
  • Tissue Inhibitor of Metalloproteinase-2
  • Metalloproteases
  • Matrix Metalloproteinase 11
  • Matrix Metalloproteinase 9