Nitric oxide synthase immunoreactivity in human bladder carcinoma

Aims-To study the expression of the endothelial and inducible isoforms of n itric oxide synthase (eNOS and iNOS, respectively) in human bladder carcino ma and schistosomal bladder disease, and to compare it with normal adult an d fetal urothelium. Nitric oxide is thought to play a complex role in human carcinogenesis, but has only recently been investigated in bladder cancer. Methods-Immunohistochemistry was performed on paraffin wax embedded section s of 33 human bladder carcinomas and five bladder carcinoma cell lines; in addition, seven schistosomal bladder cases and normal and fetal urothelium were investigated. In the cell lines enzymatic activity was examined by the NADPH diaphorase reaction. Results-Immunoreactivity for eNOS was present in most cells of all 31 cases examined. Immunoreactivity for iNOS was less abundant and was seen in 23 o f 25 cases. Similar findings were noted in schistosomal bladder cancer. In the normal bladder mucosa, eNOS immunoreactivity was found only in the supe rficial cell layer and iNOS was not expressed, whereas in the fetal urothel ium immunoreactivity for both isoforms was seen in all cell layers. Enzymat ic activity and immunoreactivity for eNOS and iNOS were evident in the five bladder carcinoma cell lines. Conclusions-It is possible that NOS plays a role in the differentiation of the transitional epithelium in fetal life, has a biological function in the adult bladder mucosa, and is involved in bladder carcinogenesis. eNOS and iNOS immunoreactivity do not differ in schistosomal and non-schistosomal bl adder carcinoma, but resemble the pattern of expression typical of fetal ur othelium.