Possible role of cyclooxygenase-2 in schistosomal and non-schistosomal-associated bladder cancer

Cyclooxygenase (COX) is an angiogenic factor that is strongly related to inflammatory diseases and the development of cancer and metastasis in several cancers. It is overexpressed in a variety of premalignant and malignant conditions, including urinary bladder cancer. Our aim was to investigate and compare the expression of COX-2 enzyme in patients with bladder cancer, chronic cystitis, and normal bladder tissue. The results were correlated to the classic prognostic factors, mainly tumor stage and grade, in a trial to determine the prognostic significance of COX-2 marker.

Seventy-five bladder samples were taken, including 50 cases with bladder cancer (31 were schistosomal-associated and 19 non-schistosomal-associated), 20 samples from cases with chronic cystitis (7 were nonschistosomal and 13 were schistosomal cystitis), and 5 samples from normal bladder tissue taken as control. The specimens were stained by streptavidin-biotin immunohistochemistry protocol, with COX-2 monoclonal antibody.

Although no notable expression of COX-2 was observed in the normal bladder, it was slightly expressed in chronic cystitis especially in areas of dysplasia and squamous metaplasia, whereas there was a significant increase in COX-2 (P < .001) with moderate-to-strong granular cytoplasmic expression in all malignant histologic types. The COX-2 reactivity was higher in transitional cell carcinoma (TCC) than in squamous cell carcinoma (SqCC) (P < .01). COX-2 expression was significantly higher in schistosomal-associated TCC than in non-schistosomal-associated TCC (P < .01). There was a statistically significant positive correlation between COX-2 expression and tumor grade (P = .0052). COX-2 expression was significantly higher in grade 3 bladder TCC than in grades 1 and 2 bladder TCC (P < .05, P < .01). A correlation between COX-2 expression and progression of bladder TCC also was observed (P = .001). There was a significant difference in COX-2 expression level between the bladder TCCs at different clinical stages (P < .01).

COX-2 is overexpressed in schistosomal-associated bladder cancer. COX-2 may be of significance to the development and proliferation of bladder TCC, consistent with a potential role for COX-2 inhibitors in the prevention and management of this disease.