The multifunctional role of the immunohistochemical expression of MMP-7 in invasive breast cancer

APMIS. 2005 Apr;113(4):246-55. doi: 10.1111/j.1600-0463.2005.apm_02.x.

Abstract

The secretion of matrix metalloproteinases (MMPs) is crucial in the metastasis of cancer cells, since MMPs are responsible for the degradation of extracellular matrix (ECM). Among them, matrix metalloproteinase-7 (MMP-7) or matrilysin 1 is a stromelysin which degrades type-IV collagen, fibronectin and laminin. Immunohistochemistry was performed to detect MMP-7 protein in infiltrative breast carcinomas. MMP-7 was studied along with clinicopathological parameters, disease-free and overall survival, and p53, c-erbB-2, topoIIa, MMP-2, uPAR and beta-catenin. MMP-7 immunoreactivity was detected in the cytoplasm of cancer cells in 54.2% (96/177) and tumor stromal cells in 47.5% (84/177), as well as in normal epithelium adjacent to malignant epithelium. MMP-7 reactivity in cancer cells displayed an inverse association with nuclear grade (p=0.049) and topoIIa (p=0.03). A parallel association was observed between the expression of MMP-7 in both malignant and stromal cells with uPAR in cancer cells (p=0.033 and p=0.027, respectively). MMP-7 of tumor stromal cells depicted a parallel correlation with MMP-2 of the same cell type (p=0.044), while abnormal beta-catenin expression was inversely associated with MMP-7 of cancer cells (p=0.047). Our results show the multifunctional role of MMP-7 in the mammary gland, since it seems to be associated with a less aggressive phenotype, while, at the same time, being involved in invasion, through its collaboration with indicators of invasion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / metabolism
  • Epithelium / metabolism
  • Female
  • Genes, erbB-2 / physiology
  • Humans
  • Immunohistochemistry
  • Mannose-Binding Lectins / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 7 / metabolism*
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Receptors, Cell Surface / metabolism
  • Stromal Cells / metabolism
  • Trans-Activators / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • beta Catenin

Substances

  • Biomarkers
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • MRC2 protein, human
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • beta Catenin
  • Matrix Metalloproteinase 7
  • Matrix Metalloproteinase 2