The prognostic value of metalloproteinases and angiogenic factors in ovarian carcinoma

Mol Cell Endocrinol. 2002 Feb 22;187(1-2):39-45. doi: 10.1016/s0303-7207(01)00709-2.


The objective of this study was to analyze the correlation between matrix metalloproteinases (MMPs) and angiogenic genes and survival in advanced-stage ovarian carcinomas. Primary and metastatic ovarian carcinomas from patients diagnosed with FIGO stage III-IV disease and followed up to 20 years were studied using mRNA in situ hybridization (ISH). Expression of MMP-2, MMP-9, membrane-type 1-MMP (MT1-MMP), the MMP inhibitor TIMP-2, vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and basic fibroblast growth factor (bFGF) was studied. MMP-2, MMP-9 and TIMP-2 mRNA was detected in both tumor and stromal cells, while MT1-MMP was largely confined to tumor cells. In univariate analysis of primary tumors, TIMP-2 and MMP-9 mRNA expression correlated with poor outcome. In metastatic lesions, mRNA expression of TIMP-2, MMP-2, and MT1-MMP correlated with poor survival. In a multivariate analysis of primary tumors, TIMP-2 expression in stromal cells (P=0.006) and MMP-9 expression in tumor cells (P=0.011) retained their predictive value. Intense expression of bFGF mRNA and weak expression of IL-8 mRNA was detected in both stromal and tumor cells in most cases, while VEGF mRNA expression was limited to a few cases. Angiogenic mRNA expression showed no correlation with disease outcome in survival analysis (P>0.05). We conclude that bFGF is the major angiogenic factor expressed in ovarian carcinoma at the mRNA level. MMP-2, MMP-9, MT1-MMP and TIMP-2 are valid markers of poor survival in advanced-stage ovarian carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inducing Agents / genetics
  • Angiogenesis Inducing Agents / metabolism*
  • Biomarkers / analysis
  • Cohort Studies
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Middle Aged
  • Nucleic Acid Hybridization
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Survivors
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Vascular Endothelial Growth Factor A*


  • Angiogenesis Inducing Agents
  • Biomarkers
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Tissue Inhibitor of Metalloproteinase-2
  • Metalloendopeptidases