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Diagnostic value of angiopoietin-2 in the differentiation of malignant pleural effusions

Year 2019, , 343 - 347, 28.05.2019
https://doi.org/10.28982/josam.555113

Abstract

Aim: Angiopoietins play an important role in the regulation of inflammation, angiogenesis and increased vascular permeability, which are the main steps in the pathogenesis of malignant pleural effusions (MPEs). The present study investigates the diagnostic value of pleural fluid angiopoietin-2 (Ang-2) levels in the differentiation of malignant pleural effusions from other effusions.

Methods: This research was designed as case-control study in a single-center. The study included a total of 66 patients (13 had transudate, 28 had benign exudate and 25 had malignant pleural effusions). The patient group involved 25 patients diagnosed with MPE, based on the criteria of lung cancer and other organ malignancies, and malignant pleural effusion. The control group consisted of 41 patients, 13 with transudate according to the Light criteria and 28 with exudate other than MPE (parapneumonic, tuberculous pleurisy, embolism, etc.). 

Results: Pleural fluid Ang-2 levels were found to be higher in both the benign and malignant exudates than in the transudative pleural effusions (P=0.001). Pleural fluid Ang-2 levels were higher in the benign exudate group than in the malignant exudate group, although the difference was not statistically significant (P=0.874). A patient with an exudative pleural effusion and a pleural fluid Ang-2 level of higher than 13.84 was found to be 1.87 times more likely to have a malignant pleural effusion.

Conclusion: Despite the use of Ang-2 levels in the differentiation of transudative and exudative pleural effusions, the present study found that Ang-2 level cannot be used to differentiate between malignant and benign exudative pleural fluids.

References

  • 1. Sahn SA. Malignant pleural effusions. In: Fishman AP (Ed). Pulmonary Diseases and Disorders. 3rd ed. Philadelphia: WB Saunders Company, 1998;1430-2.
  • 2. Yanagawa H, Takeuchi E, Suzuki Y, Ohmoto Y, Bando H, Sone S. Vascular endothelial growth factor in malignant pleural effusion associated lung cancer, Cancer Immunol Immunother, 1999;48:396-400.
  • 3. Stathopoulos GT, Kollintza A, Moschos C, Psallidas I, Sherrill TP, Pitsinos EN, et al. Tumor necrosis factor-alpha promotes malignant pleural effusion. Cancer Res. 2007;67:9825–34.
  • 4. Kim I, Moon SO, Park SK, Chae SW, Koh GY. Angiopoietin-1 reduces VEGF-stimulated leukocyte adhesion to endothelial cells by reducing ICAM-1, VCAM-1, and E-selectin expression. Circ Res. 2001;89:477-9.
  • 5. Robberts WG, Palade GE. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci. 1995;108:2369-79.
  • 6. Meurs MJ, Kümpers P, Ligtenberg J, Meertens J. Bench-to-bedside review: Angiopoietin signalling in critical illness – a future target? Crit Care. 2009;13(2):207.
  • 7. Sundberg C, Kowanetz M, Brown LF, Detmar M, Dvorak HF. Stable expression of Angiopoietin-1 and other markers by cultured pericytes: phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of Angiogenesis in vivo. Lab Invest. 2002;82:387–401.
  • 8. Fiedler U, Scharpfenecker M, Koidl S, Hegen A, Grunow V, Schmidt JM, et al. The Tie-2 ligand Angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood. 2004;103:4150–6.
  • 9. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo Angiogenesis. Science. 1997;277:55–60.
  • 10. Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zaqzaq D, et al. Vessel cooption, regression, and growth in tumors mediated by Angiopoietins and VEGF. Science. 1999;284:1994–8.
  • 11. Tait CR, Jones PF. Angiopoietins in tumours: the Angiogenic switch. J Pathol 2004;204:1-10.
  • 12. Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006;12:235–9.
  • 13. Roviezzo F, Tsigkos S, Kotanidou A, Bucci M, Brancaleone V, Cirino G, et al. Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage. J Pharmacol Exp Ther. 2005;14:738–44.
  • 14. Ayten O, Tas D, Demirer E, Okutan O, Ciftci F, Aytekin M, et al. Angiopoietin 2 levels in serum and bronchial lavage fluids and their relationship with cancer stages in lung cancer patients Thoracic Cancer. 2013;4:20–6.
  • 15. Demirer E, Oztutgan T, Tas D, Uysal A, Calışkan T, Küçükodacı Z, et al Angiopoietin 2 Tissue Immunohistochemical Staining Level And The Relation With Stage In Lung Cancer. Am. J. Respir. Crit. Care Med. 2013;187:A5519.
  • 16. Kalomenidis I, Kollintza A, Sigala I, Papapetropoulos A, Papiris S, Richard W. Light, et al. Angiopoetin-2 levels are elevated in exudative pleural effusions. Chest. 2006;129:1259-66.
  • 17. Tomimoto H, Yano S, Muguruma H, Kakiuchi S, Saburo S. Levels of soluble vascular endothelial growth factor receptor 1 elevated in the exudative pleural effusions. The journal of Medical Investigation. 2007;54:146-53.
  • 18. Elhefny RA, Shaban MM, Shaker OG. Prognostic value of pro-inflammatory cytokine and pro-Angiogenesis factor in differentiating malignant from benign exudative effusion. Clin Respir J. 2017;11(1):49-57.
  • 19. Moschos C, Psallidas I, Kollintza A, Karabela S, Papapetropoulos A, Papiris S, et al. The Angiopoietin/Tie2 axis mediates malignant pleural effusion formation. Neoplasia. 2009 Mar;11(3):298-304.
  • 20. Fang SC, Zhang HT, Hu HD, Wang CY, Zhang YM. Effect of Endostar combined with Angiopoietin-2 inhibitor on malignant pleural effusion in mice. Med Oncol. 2015 Jan;32(1):410. doi: 10.1007/s12032-014-0410-0.
  • 21. Sanad M, Shouman W, Gharib, AF. Evaluation of Serum and Pleural Levels of Angiopoietin-1 and Angiopoietin-2 in Children with Transudative and Exudative Pleural Effusions, Iran J Pediatr. 2011 Sep;21(3):278-86.

Malign plevral efüzyonların farklılaşmasında anjiyopoietin-2'nin tanısal değeri

Year 2019, , 343 - 347, 28.05.2019
https://doi.org/10.28982/josam.555113

Abstract

Amaç: Anjiopoietinler, malign plevral efüzyon (MPE) patogenezinde ana basamaklar olan inflamasyon, anjiyogenez ve vaskuler permeabilite artışının düzenlenmesinde önemli bir rol oynamaktadır. Çalışmamızda, malign plevral efüzyonların diğer efüzyonlardan ayrımında plevra sıvı anjiopoietin 2 (Ang-2) seviyelerinin tanısal değerini araştırdık.

Yöntemler: Bu çalışma, tek merkezli vaka kontrol çalışması olarak tasarlandı. Çalışmamıza, 13 transüda, 28 benign eksüda ve 25 malign plevral sıvıya sahip (malign eksüda) toplam 66 hasta alındı. Çalışmaya hasta grubu olarak olarak MPE tanısı konulmuş 25 hasta alındı. MPE tanılı hastalar; akciğer veya diğer organ maligniteleri mevcut olan ve plevral sıvının maligniteye bağlı olarak olarak geliştiği hastalardan oluştu. Kontrol grubu olarak, Light kriterlerine göre transüda olduğu saptanan 13 hasta ve MPE dışındaki eksüda vasıflı (parapnomonik, tüberküloz plörezi, emboli vb) 28 hasta olmak üzere toplam 41 hasta dahil edildi.

Bulgular: Plevral sıvı Ang-2 seviyeleri, hem benign eksüda hem de malign eksüda vasfındaki sıvılarda transüda vasfındaki plevral sıvılara göre belirgin olarak yüksek bulundu (P=0,001). Benign eksüda grubunda plevra Ang-2 seviyeleri malign eksüda grubuna göre yüksek olarak saptandı ancak bu durum istatistiksel olarak anlamlı değildi (P=0,874). Eksüda vasıflı plevral sıvılarda Ang-2 düzeyi 13,84 değerinin üzerinde saptanmış olan bir hastada malign plevral efüzyon olma riski, 13,84 değerinin altında olan bir hastaya göre 1,87 kat fazla bulundu.

Sonuç: Ang-2’nin, transüda ve eksüda özelliğindeki plevral sıvıların ayrımında kullanılabilir olmasına rağmen, eksüdatif plevral sıvılarda, malign ya da benign ayrımı yapmada yetersiz olduğu saptandı.

References

  • 1. Sahn SA. Malignant pleural effusions. In: Fishman AP (Ed). Pulmonary Diseases and Disorders. 3rd ed. Philadelphia: WB Saunders Company, 1998;1430-2.
  • 2. Yanagawa H, Takeuchi E, Suzuki Y, Ohmoto Y, Bando H, Sone S. Vascular endothelial growth factor in malignant pleural effusion associated lung cancer, Cancer Immunol Immunother, 1999;48:396-400.
  • 3. Stathopoulos GT, Kollintza A, Moschos C, Psallidas I, Sherrill TP, Pitsinos EN, et al. Tumor necrosis factor-alpha promotes malignant pleural effusion. Cancer Res. 2007;67:9825–34.
  • 4. Kim I, Moon SO, Park SK, Chae SW, Koh GY. Angiopoietin-1 reduces VEGF-stimulated leukocyte adhesion to endothelial cells by reducing ICAM-1, VCAM-1, and E-selectin expression. Circ Res. 2001;89:477-9.
  • 5. Robberts WG, Palade GE. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci. 1995;108:2369-79.
  • 6. Meurs MJ, Kümpers P, Ligtenberg J, Meertens J. Bench-to-bedside review: Angiopoietin signalling in critical illness – a future target? Crit Care. 2009;13(2):207.
  • 7. Sundberg C, Kowanetz M, Brown LF, Detmar M, Dvorak HF. Stable expression of Angiopoietin-1 and other markers by cultured pericytes: phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of Angiogenesis in vivo. Lab Invest. 2002;82:387–401.
  • 8. Fiedler U, Scharpfenecker M, Koidl S, Hegen A, Grunow V, Schmidt JM, et al. The Tie-2 ligand Angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood. 2004;103:4150–6.
  • 9. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo Angiogenesis. Science. 1997;277:55–60.
  • 10. Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zaqzaq D, et al. Vessel cooption, regression, and growth in tumors mediated by Angiopoietins and VEGF. Science. 1999;284:1994–8.
  • 11. Tait CR, Jones PF. Angiopoietins in tumours: the Angiogenic switch. J Pathol 2004;204:1-10.
  • 12. Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006;12:235–9.
  • 13. Roviezzo F, Tsigkos S, Kotanidou A, Bucci M, Brancaleone V, Cirino G, et al. Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage. J Pharmacol Exp Ther. 2005;14:738–44.
  • 14. Ayten O, Tas D, Demirer E, Okutan O, Ciftci F, Aytekin M, et al. Angiopoietin 2 levels in serum and bronchial lavage fluids and their relationship with cancer stages in lung cancer patients Thoracic Cancer. 2013;4:20–6.
  • 15. Demirer E, Oztutgan T, Tas D, Uysal A, Calışkan T, Küçükodacı Z, et al Angiopoietin 2 Tissue Immunohistochemical Staining Level And The Relation With Stage In Lung Cancer. Am. J. Respir. Crit. Care Med. 2013;187:A5519.
  • 16. Kalomenidis I, Kollintza A, Sigala I, Papapetropoulos A, Papiris S, Richard W. Light, et al. Angiopoetin-2 levels are elevated in exudative pleural effusions. Chest. 2006;129:1259-66.
  • 17. Tomimoto H, Yano S, Muguruma H, Kakiuchi S, Saburo S. Levels of soluble vascular endothelial growth factor receptor 1 elevated in the exudative pleural effusions. The journal of Medical Investigation. 2007;54:146-53.
  • 18. Elhefny RA, Shaban MM, Shaker OG. Prognostic value of pro-inflammatory cytokine and pro-Angiogenesis factor in differentiating malignant from benign exudative effusion. Clin Respir J. 2017;11(1):49-57.
  • 19. Moschos C, Psallidas I, Kollintza A, Karabela S, Papapetropoulos A, Papiris S, et al. The Angiopoietin/Tie2 axis mediates malignant pleural effusion formation. Neoplasia. 2009 Mar;11(3):298-304.
  • 20. Fang SC, Zhang HT, Hu HD, Wang CY, Zhang YM. Effect of Endostar combined with Angiopoietin-2 inhibitor on malignant pleural effusion in mice. Med Oncol. 2015 Jan;32(1):410. doi: 10.1007/s12032-014-0410-0.
  • 21. Sanad M, Shouman W, Gharib, AF. Evaluation of Serum and Pleural Levels of Angiopoietin-1 and Angiopoietin-2 in Children with Transudative and Exudative Pleural Effusions, Iran J Pediatr. 2011 Sep;21(3):278-86.
There are 21 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Research article
Authors

Dilaver Taş 0000-0003-2785-2492

Alaattin Köseler This is me 0000-0001-5835-0917

Publication Date May 28, 2019
Published in Issue Year 2019

Cite

APA Taş, D., & Köseler, A. (2019). Diagnostic value of angiopoietin-2 in the differentiation of malignant pleural effusions. Journal of Surgery and Medicine, 3(5), 343-347. https://doi.org/10.28982/josam.555113
AMA Taş D, Köseler A. Diagnostic value of angiopoietin-2 in the differentiation of malignant pleural effusions. J Surg Med. May 2019;3(5):343-347. doi:10.28982/josam.555113
Chicago Taş, Dilaver, and Alaattin Köseler. “Diagnostic Value of Angiopoietin-2 in the Differentiation of Malignant Pleural Effusions”. Journal of Surgery and Medicine 3, no. 5 (May 2019): 343-47. https://doi.org/10.28982/josam.555113.
EndNote Taş D, Köseler A (May 1, 2019) Diagnostic value of angiopoietin-2 in the differentiation of malignant pleural effusions. Journal of Surgery and Medicine 3 5 343–347.
IEEE D. Taş and A. Köseler, “Diagnostic value of angiopoietin-2 in the differentiation of malignant pleural effusions”, J Surg Med, vol. 3, no. 5, pp. 343–347, 2019, doi: 10.28982/josam.555113.
ISNAD Taş, Dilaver - Köseler, Alaattin. “Diagnostic Value of Angiopoietin-2 in the Differentiation of Malignant Pleural Effusions”. Journal of Surgery and Medicine 3/5 (May 2019), 343-347. https://doi.org/10.28982/josam.555113.
JAMA Taş D, Köseler A. Diagnostic value of angiopoietin-2 in the differentiation of malignant pleural effusions. J Surg Med. 2019;3:343–347.
MLA Taş, Dilaver and Alaattin Köseler. “Diagnostic Value of Angiopoietin-2 in the Differentiation of Malignant Pleural Effusions”. Journal of Surgery and Medicine, vol. 3, no. 5, 2019, pp. 343-7, doi:10.28982/josam.555113.
Vancouver Taş D, Köseler A. Diagnostic value of angiopoietin-2 in the differentiation of malignant pleural effusions. J Surg Med. 2019;3(5):343-7.