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

Our plain-English summary of 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, by Y. Soini, A. Puhakka, K. Kahlos, et al (Histopathology, 2001).

The study

• Authors: Y. Soini, A. Puhakka, K. Kahlos, M. Säily, P. Pääkkö, P. Koistinen, V. Kinnula
• Journal: Histopathology
• Published: 2001;39(2):179-86
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: 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.

Methods And 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.

In plain English

This laboratory study from Oulu, Finland, asked whether malignant mesothelioma tumours contain endothelial nitric oxide synthase (eNOS), an enzyme that makes nitric oxide. It also asked whether eNOS is linked to VEGF (a growth factor for blood vessels), to VEGF's two receptors FLK1 and FLT1, or to how many blood vessels a tumour has. The authors stained 36 archived malignant mesothelioma samples from Oulu University Hospital, using healthy lung and pleura as controls, and tested three cultured cell lines. Both the cultured mesothelioma cells and the non-malignant mesothelial cells made eNOS mRNA. eNOS was found in 32/36 (89%) tumours. VEGF, FLK1 and FLT1 were found in 17 (47%), 24 (67%) and 25 (69%) tumours. FLK1 and FLT1 were found more often in epithelioid and biphasic tumours than in sarcomatoid ones. FLK1, FLT1 and VEGF were not significantly associated with eNOS. None of the four markers was significantly associated with vascular density or with survival. The authors concluded that eNOS is strongly expressed in mesothelioma and may not be regulated by VEGF the way it is in endothelial cells. The study did not examine asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study: immunohistochemical staining of archived tumour samples, plus RT-PCR testing of cultured cell lines
• Who was studied: 36 malignant mesothelioma samples from the Department of Pathology, Oulu University Hospital, Finland, dated 1976 to 1999. Controls were 4 healthy lung samples and 6 histologically healthy pleura samples. Two mesothelioma cell lines (M14K, M38K) and one non-malignant mesothelial cell line (MET-5A) were also tested.
• Exposure: No exposure was studied. The study measured eNOS, VEGF, FLK1 and FLT1 in tumour tissue and vascular density (factor VIII staining). The patients' asbestos exposure is not reported.
• Main results:
  • Cultured non-malignant MET-5A mesothelial cells and cultured mesothelioma cells made eNOS mRNA, as tested by RT-PCR.
  • eNOS staining was positive in 32/36 (89%) of the malignant mesotheliomas.
  • VEGF was positive in 17 (47%) mesotheliomas, FLK1 in 24 (67%) and FLT1 in 25 (69%). These are the results-section figures; the abstract gives 45%, 69% and 71%.
  • FLK1 and FLT1 were more often expressed in epithelioid and biphasic mesotheliomas than in sarcomatoid ones (P values printed as 0.007 and 0.011).
  • FLK1 and FLT1 were associated with each other (P value printed as 0.013 in the results; the abstract gives 0.032). Neither was associated with VEGF or eNOS.
  • eNOS staining was not correlated with vascular density in the mesotheliomas.
  • FLK1 positivity was not associated with patient survival. The authors also report no association between survival and VEGF, FLT1 or eNOS, and no survival difference between sarcomatoid and epithelioid or biphasic tumours.
• The authors' conclusion: The authors concluded that eNOS is strongly expressed in malignant mesothelioma. Because eNOS was not associated with VEGF, FLK1 or FLT1, they suggested that eNOS may not be regulated by VEGF in malignant mesothelial cells in the same way as in endothelial cells.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelioma, Immunohistochemistry, Mesothelial Cells, Epithelioid, Biphasic Mesothelioma, Sarcomatoid.

Related studies

• VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours — Y. Ohta, V. Shridhar, et al. (1999)
• Expression of inducible nitric oxide synthase in healthy pleura and in malignant mesothelioma — Y. Soini, K. Kahlos, et al. (2000)
• Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma — L. Strizzi, A. Catalano, et al. (2001)
• Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells — E. Aldieri, S. Orecchia, et al. (2004)
• Regulation of nitric oxide synthase induction by iron and glutathione in asbestos-treated human lung epithelial cells — S.H. Park, A.E. Aust (1998)
• The role of endothelial nitric oxide synthase gene polymorphisms in patients with lung cancer — C. Koçer, N. Benlier, et al. (2020)

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