Stromelysin-3 protein expression in invasive breast cancer: relation to proliferation, cell survival and patients' outcome

Mod Pathol. 2002 Nov;15(11):1154-61. doi: 10.1097/01.MP.0000037317.84782.CD.

Abstract

Matrix metalloproteinases constitute one of the major extracellular matrix degrading enzymic families implicated in cancer development. Stromelysin-3 in particular, a member of the matrix metalloproteinases belonging to the stromelysins' subgroup, seems to be closely related to invasiveness and tumor progression. In this study, we proceeded to the evaluation of stromelysin-3 protein's expression in paraffin sections of 133 cases of invasive breast carcinomas and statistically estimated its relations with known clinicopathological prognostic parameters and patients' survival, proliferation markers Ki-67 and TopoIIalpha and the antiapoptotic protein bcl-2. Presence of stromelysin-3 was immunodetected, in the 73% of our cases, in stromal cells (65%) and in epithelial tumor cells (26.26%). Stromelysin-3 epithelial positivity presented statistically significant correlations with TopoIIalpha and Ki-67 proliferation indices (P =.042 and P =.031, respectively) and worse disease outcome through multivariate statistics (P =.014). Stromelysin-3 fibroblastic expression was significantly associated with nuclear grade (P =.024), ductal histological type (P =.037), TopoIIalpha (P =.001) and Ki-67 (P =.019), inversely with bcl-2 protein (P =.027) and with adverse overall survival through univariate analysis (P =.017). The subgroup of patients with stromelysin-3 co-expression in stromal and malignant epithelial cells showed statistically significant associations with Ki-67 and TopoIIalpha (P =.019, P <.0001, respectively), an inverse one with bcl-2 protein (P =.027) and furthermore with impaired survival (P =.002) through multivariate analysis. In conclusion, stromelysin-3 protein expression correlated with proliferation indices TopoIIalpha and Ki-67 and the anti-apoptotic protein bcl-2, data confirming stromelysin-3's contribution to breast cancer progression. Moreover its expression was shown to have a direct negative effect on patients' survival, especially in the subgroup of patients with simultaneous epithelial and stromal expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Division
  • Cell Survival
  • DNA Topoisomerases, Type II / analysis
  • DNA-Binding Proteins
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Matrix Metalloproteinase 11
  • Metalloendopeptidases / biosynthesis*
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Survival Analysis

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Matrix Metalloproteinase 11
  • Metalloendopeptidases
  • DNA Topoisomerases, Type II