Immunolocalization of inducible and constitutive nitric oxide synthases in human bladder cancer

Objectives. Nitric oxide (NO) is synthesized by the enzyme family of NO synthases (NOS) and plays an important role in tumor growth and angiogenesis. NO generation by inducible NOS (INOS) also influences the cytotoxicity of macrophages and tumor-induced immunosuppression. Before now, the expression of INOS and constitutive NOS in bladder carcinoma tissue had not been determined. Methods, Bladder carcinoma tissue specimens were procured from 18 patients (mean age 69.7 years) undergoing transurethral resection. In every patient, tumor biopsies were compared with biopsies of benign bladder regions. Histochemical NADPH-diaphorase staining and NOS immunohistochemistry were performed on all tissue specimens. Results. Positive NADPH-diaphorase staining was detected in all sections from bladder carcinoma tissue. NOS immunohistochemistry showed a different pattern. The malignant epithelial cells were highly iNOS positive. Specimens of bladder mucosa outside of the malignant regions showed only a weak positive iNOS immunostaining. The endothelial cells of abundant precapillary vessels in the stroma of bladder tumors showed a highly positive endothelial NOS (eNOS) immunostaining compared with the stroma of nonmalignant bladder tissue. Neuronal NOS immunoreactivity was only found in nitrinergic fibers in the fibromuscular stroma, Conclusions. Bladder carcinoma tissue had a high INOS content; benign tissue did not. NO generation from iNOS in the malignant epithelium and from eNOS in tumor stroma may play different roles in tumor angiogenesis and tumor-induced immunosuppression. (C) 1999, Elsevier Science Inc.