Activated matrix metalloproteinase-2--a potential marker of prognosis for epithelial ovarian cancer

Gynecol Oncol. 2002 Jan;84(1):126-34. doi: 10.1006/gyno.2001.6477.


Objectives and methods: To investigate the relationship between the expression of matrix metalloproteinase-2 (MMP-2) and clinical characteristics in patients with epithelial ovarian tumors, we examined the expression of MMP-2 in 26 epithelial benign ovarian tumors (EBOT) and 41 epithelial ovarian carcinomas (EOC) using semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We also analyzed pro-MMP-2 and activated MMP-2 in epithelial ovarian tumors using Western blot. RESULTS The expression levels of MMP-2 mRNA and overall protein were higher in EOC than in EBOT, but the differences were not statistically significant (P > 0.05). MMP-2 mRNA and immunoreactive protein for MMP-2 were not significantly associated with clinicopathological features in EOC. The positive percentages of the active form of MMP-2 were 71% in EOC and 42% in EBOT, respectively (P < 0.05). The positive percentage of the active form of MMP-2 in stage III and IV EOC was significantly higher (81%) than that (33%) in stage I and II EOC (P = 0.01). The expression of activated MMP-2 was significantly related to disease progression in EOC (P = 0.02). The percentages of active MMP-2 in positive immunoreaction tumor cells and fibroblasts were, respectively, 96 and 89%. The difference was not statistically significant (P = 0.54). The positive and negative predictive values of active MMP-2 for disease progression were 65 (19/29) and 75% (9/12), respectively, and the accuracy was 68% (28/41).

Conclusion: MMP-2 generally appears in epithelial ovarian tumors and there is a tendency to express more MMP-2, and especially activated MMP-2, in EOC. MMP-2 mRNA and pro-MMP-2 are not associated with the clinicopathological features in patients with EOC. There was a significant relationship between activated MMP-2 and invasiveness, metastasis, and disease progression in EOC and activated MMP-2 is a potential marker of prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Enzyme Activation
  • Enzyme Precursors / biosynthesis
  • Enzyme Precursors / metabolism
  • Epithelial Cells / pathology
  • Female
  • Gelatinases / biosynthesis
  • Gelatinases / metabolism
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Metalloendopeptidases / biosynthesis
  • Metalloendopeptidases / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • Biomarkers, Tumor
  • Enzyme Precursors
  • RNA, Messenger
  • Gelatinases
  • Metalloendopeptidases
  • progelatinase
  • Matrix Metalloproteinase 2