Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in uterine endometrial carcinoma and a correlation between expression of matrix metalloproteinase-7 and prognosis

Int J Mol Med. 2005 Oct;16(4):541-6.


Matrix metalloproteinases (MMPs) are associated with invasion and metastasis of several human malignant tumors, in particular MMP-7, which is mainly produced by the cancer cell itself. We examined the expression of MMP-2, 7 and 9, and tissue inhibitors of metalloproteinase (TIMP)-1 and 2 in uterine endometrial carcinoma, and compared the expression with clinicopathological characteristics in uterine endometrial carcinoma (UEC). A group of 256 patients with UEC received surgery at the Osaka City University Medical School Hospital, and 196 tumor samples were immunohistochemically stained to examine the expression of MMP-2, 7 and 9, and TIMP-1 and 2. Additionally, the invasion ability of cell stain established from UEC was examined using an in vitro invasion assay. The expression of MMP-2, 7 and 9, and TIMP-1 and 2 was observed in the cytoplasm, and the expression of MMP-2 and 7, and TIMP-1 and 2 was observed in stromal cells around the tumor cells. The expression of MMP-7 was significantly stronger in higher-grade than lower-grade tumors (P<0.05). The invasion assay showed that the invasion of cells derived from UECs was significantly inhibited by TIMP-1 and 2. The disease-free interval was significantly shorter when MMP-7 expression was intense. This increased expression of MMP-7 in high grade UECs may be associated with tumor invasion and metastasis, and MMP-7 could serve as a prognostic maker in UEC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Cell Movement
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 7 / biosynthesis*
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinases / biosynthesis*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis
  • Tissue Inhibitor of Metalloproteinases / biosynthesis*
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / pathology*


  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinases
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 7
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9