title: Enhanced expression of cyclooxygenase-2 in high grade human transitional cell bladder carcinomas.
abstract: Studies in human and animal models have shown that cyclooxygenase (COX)-2 is up-regulated in several epithelial carcinomas including colon, breast, and lung. To elucidate the possible involvement of COX-2 in human bladder cancer we examined the expression of COX isoforms in benign tissue and in bladder carcinoma specimens. Paraffin embedded tissues from 75 patients with urothelial carcinomas were immunostained with specific antibodies raised against COX-1 and COX-2. COX-1 expression was detected in smooth muscle cells in both benign and malignant bladders. COX-2 immunoreactivity was absent in benign tissue and in specimens with low-grade urothelial carcinoma (0/23). In contrast, expression of COX-2 was detected in malignant epithelial cells in 38% (17/47) of specimens with high-grade urothelial carcinomas. Expression of COX-2 in high-grade bladder cancer was confirmed by radioactive in situ hybridization using a COX-2-selective riboprobe. Both immunohistochemistry and in situ hybridization showed COX-2 expression in a small subset of malignant cells. COX-2 mRNA was also expressed in three out of seven malignant urothelial cell lines. These data demonstrate elevated expression of COX-2 in a high percentage of high-grade bladder carcinomas, suggesting a possible role of COX-2 in the progression of bladder urothelial carcinoma and supporting its potential as a therapeutic target in human bladder carcinoma.
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kömhoff
authors.forename: Y
authors.initials: Y
authors.lastname: Guan
authors.forename: H W
authors.initials: HW
authors.lastname: Shappell
authors.forename: L
authors.initials: L
authors.lastname: Davis
authors.forename: G
authors.initials: G
authors.lastname: Jack
authors.forename: Y
authors.initials: Y
authors.lastname: Shyr
authors.forename: M O
authors.initials: MO
authors.lastname: Koch
authors.forename: S B
authors.initials: SB
authors.lastname: Shappell
authors.forename: M D
authors.initials: MD
authors.lastname: Breyer
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D009367:Neoplasm Staging; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000201:enzymology / Q000473:pathology
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases