Expression of inducible nitric oxide synthase in bone metastases

Aims: The signalling molecule nitric oxide (NO), produced predominantly in cancer by the enzyme inducible NO synthase (iNOS), has been implicated in the pathophysiology of many human tumours. The increased NO concentrations found in many human cancers may facilitate both angiogenesis and tumour dissemination. NO also plays a concentration-dependent role in bone re-modelling by acting on osteoclasts. Although iNOS has been studied extensively in most primary tumours, there are no reports that have investigated its expression in metastatic bone disease. Methods: An immunohistochemical study was performed using a monoclonal antibody to iNOS in 27 cases of breast, renal and lung bone metastases, biopsied at the time of treatment for pathological fracture. Results: iNOS expression was found in 14 cases and was predominantly localised to tumour cells in the metastatic deposits. A significant difference was found between iNOS expression in metastases and adjacent bone (p<0.001), where immunostaining was rarely seen and confined to immune cells. No microscopic differences in bone architecture could be seen between iNOS positive and negative metastases, and no correlations were found between iNOS expression and clinico-pathological variables. Conclusions: iNOS expression is not a pathognomonic finding in bone metastasis. Its role in the behaviour of bone metastases requires further investigation.