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.
OBJECTIVE
To investigate endothelial nitric oxide synthase (eNOS) expression in malignant mesothelioma and its association with expression of vascular endothelial growth factor (VEGF), its receptors FLK1 and FLT1, and vascular density.


RESULTS
eNOS, VEGF, FLK1 and FLT1 were studied in 36 histological mesothelioma samples by immunohistochemistry. Two mesothelioma (M14K, M38K) and one non-neoplastic mesothelial cell line (MET-5A) were studied for eNOS mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). Vascular density was determined by staining the samples with an antibody to factor VIII. RT-PCR showed that mesothelioma cells synthesize eNOS in vitro. eNOS immunoreactivity was found in 32/36 (89%) tumours. VEGF, FLK1 and FLT1 expression was found in 17 (45%), 24 (69%) and 25 (71%) cases, respectively. FLK1 or FLT1 immunoreactivity was more often seen in epithelioid 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 between FLK1, FLT1, VEGF and eNOS immunoreactivity and vascular density.


CONCLUSIONS
eNOS is strongly expressed in malignant mesothelioma. Since eNOS 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.
Soini
Y
Y
Department of Pathology, University Hospital, University of Oulu, PO Box 5000 (Aapistie 5), FIN-90014 Oulu, Finland. msoini@cc.oulu.fi
Puhakka
A
A
Kahlos
K
K
Säily
M
M
Pääkkö
P
P
Koistinen
P
P
Kinnula
V
V
D000328:Adult; D000368:Aged; D001808:Blood Vessels / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000032:analysis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000032:analysis; D008297:Male; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000032:analysis* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D011506:Proteins / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1