Endothelial nitric oxide synthase is strongly expressed in malignant mesothelioma but does not associate with vascular density or the expression of VEGF, FLK1 or FLT1

Aims: To investigate endothelial nitric oxide synthase (eNOS) expression in malignant mesothelioma and its association with expression of vascular end othelial growth factor (VEGF), its receptors FLK1 and FLT1, and vascular de nsity. Methods and results: eNOS, VEGF, ELK1 and FLT1 were studied in 36 histologi cal mesothelioma samples by immunohistochemistry. Two mesothelioma (M14K, M 38K) and one non-neoplastic mesothelial cell line (MET-5A) were studied for eNOS mRNA expression by reverse transcriptase-polymerase chain reaction (R T-PCR). Vascular density was determined by staining the samples with an ant ibody to factor VIII. RT-PCR showed that mesothelioma cells synthesize eNOS in vitro. eNOS immunoreactivity was found in 32/36 (89%) tumours. VEGF, FL K1 and FLT1 expression was found in 17 (45%), 24 (69%) and 25 (71%) cases, respectively. FLK1 or FLT1 immunoreactivity was more often seen in epitheli oid and biphasic mesotheliomas than in sarcomatoid ones (P = 0.007 and P = 0.011, respectively). There was a significant association between FLK1 and FLT1 immunoreactivity (P = 0.032). No significant association was found bet ween FLK1, FLT1, VEGF and eNOS immunoreactivity and vascular density. Conclusions: eNOS is strongly expressed in malignant mesothelioma. Since eN OS did not associate with VEGF, FLK1 or FLT1, its synthesis seems not to be regulated through VEGF in malignant mesothelioma as has been shown in non- neoplastic endothelial cells.