Significance Of Cyclooxygenase-2 In Human Renal Cell Carcinoma, Bladder Transitional Cell Carcinoma And Exfoliated Urothelial Cells Of Bladder Cancer

Objective: Epidemiological studies have suggested that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of gastric and colorectal cancer. Animal studies demonstrated that NSAIDs can suppress intestinal polyposis in APC mutant mice, a model of human familial adenomatous polyposis, and inhibit carcinogenesis in several rodent models including those of bladder cancer. In addition, NSAIDs can induce regression of premalignant colorectal polyps in patients with familial adenomatous polyposis. The best known target of NSAIDs is cyclooxygen- ase-2(Cox-2), which may be the inhibitory mechanisms. Cox is the rate-limiting enzyme in the conversion of arachidonic acid to prostanoids, and it produces prostaglandin H2 from arachidonic acid, which is catalyzed to various prostaglandin in normal and pathologic conditions. Recently studies have suggested that COX-2 is overexpressed in several tumor tissues, such as colon carcinoma, gastric carcinoma, breast carcinoma, hepatocellular carcinoma, lung carcinoma, esophageal carcinoma, and pancreatic carcinoma. However,there are little data demonstrate elevated expression of COX-2 in tumours in urology. The aim of the present study was to investigate the significance of expression of COX-2 in human transitional cell carcinomas(TCCs) of the urinary bladder, and to evaluate the value of COX-2 expression in exfoliated urothelial cells in early diagnosis, and to explore the expression of COX-2 in human renal cell carcinomas(RCCs). Materials and Methods: The expression of COX-2 in human TCCs of the urinary bladder was observed with immunohistochemical methods and COX-2 immunocytology were performed on exfoliated urothelial cells in the patients with TCC and 30 subjects with normal urothelium. The expression of COX-2 was observed in 35 RCCs by immunohistochemical staining of SP methods.Results: We found that COX-2 predominates in tumor tissues of human transitional cell carcinomas(TCCs) of the urinary bladder and human renal cell carcinomas(RCCs). Renal COX-2 was localized in the macula densa (MD) and associated cortical thick ascending limb (cTALH) and medullary interstitial cells (MICs), which was very weak. The normal transitional cell epithelium and the stroma of the bladder carcinomas was virtually negative for COX-2. 1. COX-2 specific proteins were found in 24 of 35 RCC specimens, while in control renal tissues were 4 of 20. Expression of COX-2 in RCCs was significantly higher thanthat in control renal tissues(χ2=10.1, P＜0.05). The rate of COX-2 positivity in different stage PT1, PT2, PT3, PT4 was 55.6％(5／9), 57.1％(8／14), 85.7％(6／7) and 100％(5／5) respectively. There are statistical significances between the PT1-2 and PT3-4 stage cases(P=0.036, Fisher exact probabilities), but no correlation was found between COX-2 and tumor grading. 2. COX-2 specific proteins were found in 35 of 48 TCC specimens but not in control urinary bladder tissues. The rate of COX-2 positivity in different stage Ta-1 and T2-4 was 63.6％(21／33) and 93.3％(14／15) respectively. There are statistical significances between the Ta-1 and T2-4 stage cases(P=0.031, Fisher exact probabilities), but no correlation was found between COX-2 and tumor grading. 3. The normal urothelium in nonneoplastic patients was negative for COX-2. The positive staining of COX-2 in exfoliated urothelial cells of patients with TCC was 67.5％, which was significantly higher than the positive rate of cytopathology (37.5％)(χ2=7.22,P＜0.05). Especially in low grade(G1) and low stage(Ta～T1) cancer, the positive staining of COX-2 in exfoliated urothelial cells was 52.9％and 57.6％ respectively, while the positive rate of cytopathology was 11.8％ and 26.9％, there are statistical significances (P=0.013,Fisher exact probabilities;χ2=5.04, P＜0.05).Conclusions: The results of the current study demonstrated that: 1. Expression of COX-2 in RCCs was significantly higher than that in normal renal tissues. There are statistical significances between different st...