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

Purpose: This study was conducted to clarify which matrix metalloproteinase s (MMPs) play a key role in destruction of the underlying basement membrane (BM) of superficial urothelial carcinomas. Urine concentrations of MMP-9 a nd tissue inhibitors of matrix metalloproteinase-l (TIMP-1) were also measu red. Materials and Methods: Overexpression of MMP-1, MMP-2 and MMP-9 was analyze d immunohistochemically in 60 patients with transitional cell carcinomas of the urothelium (41 were pTa or pis, 19 were pT(1-4)), and compared them wi th type IV collagen expression in tumor BM. In 33 of them, urine concentrat ions of MMP-9 and TIMP-1 were measured by one-step sandwich enzyme immunoas say. 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 increa sed with grades and stages (p = 0.03). In pTa and pis tumors, type IV colla gen 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 sam ples of urothelial cancer patients, while urine TIMP-1 was detectable in 18 of 33 patients. In 16 healthy volunteers, both of them were below detectab le 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 invas ion step of superficial urothelial carcinomas. Detection of urinary MMP-9 m ay become a new, non-invasive mean for the diagnosis of urothelial carcinom as.