Expression of inducible nitric oxide synthase in healthy pleura and in malignant mesothelioma

In this study we investigated the immunohistochemical expression of inducib le nitric oxide synthase (iNOS) in a set of normal pleural mesothelial tiss ues, malignant mesotheliomas, mesothelioma cell lines and metastatic pleura l adenocarcinomas. Furthermore, the expression of mRNA was assessed in four malignant mesothelioma cell lines in culture. Apoptosis and vascular densi ty in malignant mesotheliomas was assessed by the TUNEL method and by immun ohistochemistry with an antibody against FVIII-related antigen. Immunohisto chemically mesothelial cells in non-neoplastic healthy pleural tissues were mostly negative for iNOS. Positivity for iNOS was observed in 28/38 (74%) and 24/25 (96%) of malignant mesotheliomas and metastatic pleural adenocarc inomas. respectively Epithelial and mixed mesotheliomas expressed more ofte n strong iNOS immunoreactivity compared to the sarcomatoid subtype (P = 0.0 23). Moreover, metastatic adenocarcinomas expressed more often iNOS positiv ity than mesotheliomas (P = 0.021). Experiments with the cell lines confirm ed that malignant mesothelioma cells are capable of synthesizing iNOS. No s ignificant association was found between iNOS expression and apoptosis or v ascular density in malignant mesotheliomas. The higher expression of iNOS i n the epithelial subtype of mesothelioma and pleural metastatic adenocarcin oma might be due to an increased sensitivity of these cell types to cytokin e-mediated iNOS upregulation. The strong expression of iNOS suggests a puta tive role for NO in the growth and progression of these tumours. (C) 2000 C ancer Research Campaign.