Immunolocalization of inducible and constitutive nitric oxide synthases inhuman bladder cancer

Objectives. Nitric oxide (NO) is synthesized by the enzyme family of NO syn thases (NOS) and plays an important role in tumor growth and angiogenesis. NO generation by inducible NOS (INOS) also influences the cytotoxicity of m acrophages and tumor-induced immunosuppression. Before now, the expression of INOS and constitutive NOS in bladder carcinoma tissue had not been deter mined. 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. Hist ochemical NADPH-diaphorase staining and NOS immunohistochemistry were perfo rmed on all tissue specimens. Results. Positive NADPH-diaphorase staining was detected in all sections fr om bladder carcinoma tissue. NOS immunohistochemistry showed a different pa ttern. The malignant epithelial cells were highly iNOS positive. Specimens of bladder mucosa outside of the malignant regions showed only a weak posit ive iNOS immunostaining. The endothelial cells of abundant precapillary ves sels in the stroma of bladder tumors showed a highly positive endothelial N OS (eNOS) immunostaining compared with the stroma of nonmalignant bladder t issue. Neuronal NOS immunoreactivity was only found in nitrinergic fibers i n the fibromuscular stroma, Conclusions. Bladder carcinoma tissue had a high INOS content; benign tissu e did not. NO generation from iNOS in the malignant epithelium and from eNO S in tumor stroma may play different roles in tumor angiogenesis and tumor- induced immunosuppression. (C) 1999, Elsevier Science Inc.