Prostaglandin receptors EP1-4 as a potential marker for clinical outcome in urothelial bladder cancer.

Prostaglandins, especially prostaglandin E2 (PGE2), and COX-2 play an important role in carcinogenesis of many tumors including bladder cancer (BCA). The PGE2 receptors EP1-4 regulate tumor cell growth, invasion and migration in different tumor entities but EP expression in BCA remains to be determined. In the present study we examined the expression of EP1-4 in non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and normal urothelial tissue (NU) using immunohistochemistry. Nuclear and cytoplasmic EP1-4 expression was correlated with clinicopathological parameters and survival of BCA patients. EP1, EP2 and EP3 were significantly less expressed in the cytoplasm und nucleus of NMIBC and MIBC than in NU; EP4 cytoplasmic staining in MIBC was significantly higher compared to NU. The cytoplasmic staining was significantly more abundant in MIBC than in NMIBC in all investigated receptors except EP2. The level of EP staining in NMIBC was correlated with staging and grading, especially cytoplasmic EP1. Nuclear staining of EP1 was an independent predictor of BCA recurrence-free survival in NMIBC patients. EP receptors are dysregulated in BCA. The increase of EP1 may be used as prognostic parameter in NMIBC patients and its dysregulation could be targeted by specific EP1 inhibitors.