Localization and expression of tissue inhibitor of metalloproteinase-1 in human urothelial cancer.
OBJECTIVE
We evaluated the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the invasion and metastasis of human urothelial cancer.


METHODS
The expression level of TIMP-1 messenger (m)RNA was determined in 33 urothelial carcinomas, including upper urothelial cancer in 15 cases and bladder cancer in 18, by Northern blot analysis. Localization of TIMP-1 mRNA was analyzed by in situ hybridization. These data were compared with clinicopathological features. We also determined the growth activity of tumor cells using immunohistochemical staining for Ki-67 and compared it with the expression levels of TIMP-1 mRNA. These data were also compared with clinicopathological features.


RESULTS
The expression level of TIMP-1 mRNA significantly correlated with pathological stage and histological differentiation. In situ hybridization showed that TIMP-1 mRNA was expressed in the cytoplasm of urothelial cancer cells. The Ki-67 labeling index significantly correlated with the expression level of TIMP-1 mRNA in urothelial cancer. Patients with high expression of TIMP-1 mRNA had a poorer prognosis than those with low expression.


CONCLUSIONS
TIMP-1 mRNA is expressed in the cytoplasm of cancer cells and high expression indicates more malignant potential in cases of urothelial cancer.
Yano
Akira
A
Department of Urology, Hiroshima University Faculty of Medicine, Minami-ku, Hiroshima, Japan.
Nakamoto
Takahisa
T
Hashimoto
Kunihiro
K
Usui
Tsuguru
T
D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D014571:Urologic Neoplasms / Q000378:metabolism* / Q000473:pathology
D019394:Ki-67 Antigen; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1