Overexpression of cyclooxygenase-2 in high-grade human transitional cell carcinoma of the upper urinary tract

To examine cyclooxygenase (COX)-2 expression (a key enzyme in the synthesis of prostaglandins, and involved in carcinogenesis of human epithelial tumours) in human transitional cell carcinomas (TCCs) of the renal pelvis and ureter, and to determine whether COX-2 expression correlates with the clinicopathological characteristics of the disease. Specimens from 144 patients with TCC of the upper urinary tract who had undergone nephroureterectomy were analysed immunohistochemically, and 23 were also analysed by immunoblotting. Immunoblot analysis showed COX-2 immunoreactivity in 17 (74%) of 23 tumours, but not in normal transitional epithelium. COX-2 was localized to the cytoplasm of cancer cells and expressed in 108 (75%) of 144 tumours, as assessed by immunohistochemical analysis. COX-2 expression correlated with tumour grade (P < 0.008), being detected in one of nine grade 1, 77 (79%) of 97 grade 2 and 30 (79%) of 38 grade 3 tumours. Other variables including tumour stage were not associated with COX-2 expression. We show for the first time that COX-2 is frequently expressed in TCC of the upper urinary tract and is associated with the degree of tumour cell differentiation, indicating that COX-2 may be involved in TCC carcinogenesis at an early and/or late stage, and could be a useful target for chemoprevention of this type of cancer.