Differential expression of MMP and uPA systems and prognostic relevance of their expression in esophageal squamous cell carcinoma

Int J Cancer. 2004 Jun 10;110(2):201-7. doi: 10.1002/ijc.20067.

Abstract

Matrix metalloproteinase (MMP) is critical for carcinoma progression. In our study, we evaluated the prognostic significance of the major MMP family such as MMP-3, MMP-9, MMP-11 and MT1-MMP at the mRNA in 44 esophageal squamous cell carcinoma (ESCC) that were previously characterized for MMP-7, MMP-1 and MMP-2, and their relation to urokinase system (uPA and uPAR). MT1-MMP, MMP-11 and MMP-2 expressions are closely associated with each other, while MMP-9 and uPAR expressions are inversely associated with the former group. There is no MMP related to clinicopathological factors; however, patients with high MT1-MMP could show worse prognosis, as compared to those with low MT1-MMP expression (p=0.01), as well as MMP-11 did (p=0.02). Both MMP showed clear expression of carcinoma cells by immunohistochemistry. In patients with high MT1-MMP, recurrence was more prominent (23/26: 88.5%) than those with low MT1-MMP (7/18: 38.9%) (p=0.0016). In the 20 cases who died within 3 years, all 15 cases with high MT1-MMP showed initial recurrence of distant metastasis, and the other 5 cases with low MT1-MMP showed locoregional recurrence (p=0.000064). These results could indicate that there is a relevant mechanism of associated expression of clinically significant MMP and that among them, MT1-MMP plays the most critical role in ESCC progression.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 11
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / physiology
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / physiology
  • Matrix Metalloproteinases / genetics*
  • Matrix Metalloproteinases / physiology
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / physiology
  • Middle Aged
  • Prognosis
  • Survival Rate
  • Urokinase-Type Plasminogen Activator / genetics*

Substances

  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 11
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9