Enhanced expression of cyclooxygenase-2 in high grade human transitional cell bladder carcinomas

Studies in human and animal models have shown that cyclooxygenase (COX)-2 i s up-regulated in several epithelial carcinomas including colon, breast, an d lung. To elucidate the possible involvement of COX-2 in human bladder can cer we examined the expression of COX isoforms in benign tissue and in blad der carcinoma specimens. Paraffin embedded tissues from 75 patients with ur othelial carcinomas were immunostained with specific antibodies raised agai nst COX-1 and COX-2. COX-I expression was detected in smooth muscle cells i n 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, Express ion of COX-2 in high-grade bladder cancer was confirmed by radioactive in s itu hybridization using a COX-2-selective riboprobe, Both Immunohistochemis try and ill situ hybridization showed COX-2 expression in a small subset of malignant cells. COX-2 mRNA was also expressed In three out of seven malig nant urothelial cell lines, These data demonstrate elevated expression of C OX-2 In a high percentage of high-grade bladder carcinomas, suggesting a po ssible role of COX-2 In the progression of bladder urothelial carcinoma and supporting its potential as a therapeutic target in human bladder carcinom a.