Role of matrix metalloproteinase-9 in the basement membrane destruction of superficial urothelial carcinomas

J Urol. 1999 Apr;161(4):1359-63.


Purpose: This study was conducted to clarify which matrix metalloproteinases (MMPs) play a key role in destruction of the underlying basement membrane (BM) of superficial urothelial carcinomas. Urine concentrations of MMP-9 and tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) were also measured.

Materials and methods: Overexpression of MMP-1, MMP-2 and MMP-9 was analyzed immunohistochemically in 60 patients with transitional cell carcinomas of the urothelium (41 were pTa or pis, 19 were pT1-4), and compared them with type IV collagen expression in tumor BM. In 33 of them, urine concentrations of MMP-9 and TIMP-1 were measured by one-step sandwich enzyme immunoassay.

Results: Positive expression of MMP-1, MMP-2 and MMP-9 was found in 53%, 17%, and 65% of tumors, respectively. Only MMP-9 expression rates were increased with grades and stages (p = 0.03). In pTa and pis tumors, type IV collagen expression was reduced in 17 of 26 (65.4%), and it was associated with positive MMP-9 expression (p = 0.0283). MMP-9 was detected in all urine samples of urothelial cancer patients, while urine TIMP-1 was detectable in 18 of 33 patients. In 16 healthy volunteers, both of them were below detectable levels. Balance between urinary MMP-9 and TIMP-1 were particularly kept in superficial urothelial carcinomas with intact tumor BM. Tumor BM status, however, was not associated with urinary MMP-9 or TIMP-1 levels.

Conclusions: These results suggest that MMP-9 plays a key role in the invasion step of superficial urothelial carcinomas. Detection of urinary MMP-9 may become a new, non-invasive mean for the diagnosis of urothelial carcinomas.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Basement Membrane / pathology
  • Carcinoma, Transitional Cell / enzymology*
  • Carcinoma, Transitional Cell / pathology*
  • Carcinoma, Transitional Cell / urine
  • Collagenases / physiology*
  • Collagenases / urine
  • Gelatinases / physiology
  • Gelatinases / urine
  • Humans
  • Matrix Metalloproteinase 1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / physiology
  • Metalloendopeptidases / urine
  • Middle Aged
  • Urinary Bladder Neoplasms / enzymology*
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / urine


  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1