EXPRESSION OF CYCLOOXYGENASE-2 AND EP4 RECEPTOR IN TRANSITIONAL CELL CARCINOMA OF THE UPPER URINARY TRACT

Abstract

Prostaglandin E2, produced by cyclooxygenase (COX)-2, affects the behavior of tumor cells possibly through 1 of the prostaglandin E2 receptors, the EP4 receptor (EP4R). The relationship between tumor development and EP4R in transitional cell carcinoma of the upper urinary tract (TCC-UUT) has not been fully understood. We determined the relationships between clinicopathological features and prognosis with expressions of COX-2 and EP4R in nonmetastatic TCC-UUT. We examined expressions of COX-2 and EP4R by immunohistochemical technique in 101 patients. Histological features including tumor grade, pT stage and lymph node metastasis were examined using formalin fixed and paraffin embedded specimens from the radical operation. The predictive values of these expressions of prognosis were investigated by Kaplan-Meier curve and Cox proportional hazards analysis in multivariate model. Expression of COX-2 and EP4R was observed in 46 (45.5%) and 51 (50.5%) cases, respectively. Each expression was significantly associated with pT stage and grade. Patients with co-expression of these proteins had a higher frequency of extra-urinary tract recurrence (33.3%). Postoperative survival time of patients with co-expression of COX-2 and EP4R was significantly shorter than that of patients with other expression patterns (p <0.001). Although COX-2 or EP4R expression was not an independent factor for cause specific survival in a multivariate model, co-expression of these proteins was an independent one (odds ratio 12.26 and p = 0.0038). Co-expression of COX-2 and EP4R is a potentially useful marker for tumor progression and survival in patients with nonmetastatic TCC-UUT.