Expression of MMP-1, MMP-9 and TIMP-2 in prostate carcinoma and their influence on prognosis and survival

J Cancer Res Clin Oncol. 2013 Aug;139(8):1373-82. doi: 10.1007/s00432-013-1453-x. Epub 2013 May 25.

Abstract

Purpose: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) participate in tumorigenesis, and their association with disease outcome is highly controversial. The present study investigates the influence of MMP-1, MMP-9 and TIMP-2 on different clinicopathologic variables and disease-free survival (DFS) of patients with prostate carcinoma.

Methods: Hundred and forty-five cases are included in the study, and levels of MMP/TIMP expressions are assessed in three tissue compartments (i.e., tumor, stroma and normal glands) with immunohistochemistry.

Results: Matrix metalloproteinase-1 expression in tumor cells was associated with lower Gleason scores, pretreatment prostate-specific antigen levels and lower incidence of vascular, perineural and extracapsular invasions. Moreover, MMP-9 positivity and TIMP-2 expression in normal glands were correlated with lower Gleason patterns and early stage at presentation. Expression of MMP in tumor cells and the presence of TIMP-2 in normal glands were associated with better DFS.

Conclusion: Variability of MMP/TIMP expressions from case to case makes it difficult to evaluate their impact on clinical outcome. However, these proteins might be new and promising targets for prostate cancer therapy in the future.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Carcinoma / enzymology*
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Disease-Free Survival
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Matrix Metalloproteinase 1 / analysis
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 9 / analysis
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Tissue Array Analysis
  • Tissue Inhibitor of Metalloproteinase-2 / analysis
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis*

Substances

  • Biomarkers, Tumor
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • MMP1 protein, human
  • Matrix Metalloproteinase 1