Expression patterns of stromal MMP-2 and tumoural MMP-2 and -9 are significant prognostic factors in invasive ductal carcinoma of the breast

APMIS. 2014 Dec;122(12):1196-206. doi: 10.1111/apm.12285. Epub 2014 Jun 7.

Abstract

Matrix metalloproteinases (MMPs) are matrix-degrading enzymes that play a pivotal role in aggressive behaviours, such as rapid tumour growth, invasion, and metastasis, of several types of solid tumours. In particular, stromal MMP-2 plays important roles in the progression of malignant tumours, but most clinical studies have focused on tumoural MMP-2 and -9 expression, and not stromal MMP-2 expression. One hundred and seventy-seven cases diagnosed as invasive ductal carcinoma of the breast between 2000 and 2005 were included in this study. Expressions of tumoural MMP-2 and -9 and stromal MMP-2 were analysed by immunostaining on a tissue microarray. Subsequently, the associations between those results and various clinicopathological parameters were evaluated. Stromal MMP-2 expression correlated significantly with clinicopathological parameters such as advanced T category, larger tumour size, high histological grade, tumour necrosis, ER- and PR-negative, and HER-2-positive (all p < 0.05). In univariate and multivariate analyses, overall survival was linked with stromal MMP-2 expression as well as dual expression of stromal MMP-2 and tumoural MMP-2 and -9 (all p < 0.05). Stromal MMP-2 expression may play a crucial role in predicting aggressive clinical behaviour in breast cancer patients.

Keywords: MMP2; MMP9; breast; invasive ductal carcinoma; stromal cell.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Ductal, Breast / diagnosis*
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism

Substances

  • Biomarkers, Tumor
  • Receptor, ErbB-2
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9