Bilharzial vs non-bilharzial related bladder cancer: Pathological characteristics and value of cyclooxygenase-2 expression

Bilharziasis is the reason for the high incidence of bladder cancer in Egypt. Some of the clinico-pathological characteristics of bilharzia-associated bladder cancer has been published before. This paper adds insight about the biology of the disease. COX-2 shows usefulness as a prognostic marker for bilharzia-associated bladder cancer, which might open avenues for preventive and therapeutic strategies utilizing COX-2 inhibitors in the management of bladder cancer arising on top of chronic inflammation. OBJECTIVE • To assess the expression pattern of cyclooxygenase-2 (COX-2) in bilharzial and non-bilharzial related bladder cancer (BBC and NBBC) and its association with clinical outcome after radical cystectomy (RC). We also determined the clinico-pathological differences between BBC and NBBC. PATIENTS AND METHODS • Immunohistochemical (IHC) staining for COX-2 was performed on archival bladder specimens from 315 patients treated with RC between 1997 and 2003. • Patients were divided into 2 groups: Group 1 comprised 205 patients (65%) with BBC and group 2 comprised 110 patients (35%) with NBBC. • Clinico-pathological differences were compared and altered IHC expression of COX-2 was correlated with clinical outcome in both groups. RESULTS • The study included 315 patients (239 males and 76 females) with median age 54 y (range 31-79) and median follow up of 63.2 months after RC. • There was significant difference in histological types, tumor stage, grade, and architecture and COX-2 alterations between both groups (P < 0.05). • BBC presented with lower grade, higher stage, and non-papillary non-urothelial carcinoma. COX-2 overexpression was associated with pathological T stage (P= 0.01), grade (P < 0.001) and lymphovascular invasion (LVI) (P= 0.041). • COX-2 expression was an independent predictor of disease recurrence (HR 1.9, CI 0.99-3.626 and P= 0.05) and cancer specific mortality (HR 2.8, CI 1.155-6.73 and P= 0.023) only in BBC but not in NBBC (HR 1.6, CI 0.598-4.364, P= 0.344 and HR 0.349, CI 0.076-1.595, P= 0.175, respectively). CONCLUSIONS • BBC differs pathologically and biologically from NBBC. BBCs present more frequently as low-grade, high stage non-papillary and non-urothelial cancers. BBCs with COX-2 alterations are associated with worse outcome after RC. • Our findings support the need for further evaluation of COX-2 and inflammatory signaling pathways as well as COX-2-targeted prevention and therapies in BC.