NITRIC-OXIDE SYNTHASE ACTIVITY IN HUMAN BREAST-CANCER

Nitric oxide (NO) is generated by a family of isoenzymes (NO synthases ) expressed in a wide range of mammalian cells. We have recently repor ted NO synthase expression in human gynaecological cancers. In this st udy we have assessed the activity and distribution of NO synthase in a series of human breast tumours and in normal breast tissue. Calcium-d ependent (constitutive) and -independent (inducible) NO synthase activ ity, as well as NO biosynthesis, was high in invasive tumours compared with benign or normal tissue. Furthermore, for invasive ductal carcin omas, NO biosynthesis was significantly greater for grade III compared with grade II tumours. Immunohistochemical investigations revealed im munolabelling with a monoclonal antibody to murine inducible NO syntha se predominantly within tumour-associated macrophages. Immunolabelling with a polyclonal antiserum raised against rat brain NO synthase was also observed in vascular endothelial and myoepithelial cells. Thus NO synthase is expressed in human breast tumours, where its presence cor relates with tumour grade.