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

Authors

Keywords:

Angiopoietin-2, Malignant pleural effusion, Exudative pleural effusion

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.

Downloads

Download data is not yet available.

References

Sahn SA. Malignant pleural effusions. In: Fishman AP (Ed). Pulmonary Diseases and Disorders. 3rd ed. Philadelphia: WB Saunders Company, 1998;1430-2.

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.

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.

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.

Robberts WG, Palade GE. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci. 1995;108:2369-79.

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.

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.

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.

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.

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.

Tait CR, Jones PF. Angiopoietins in tumours: the Angiogenic switch. J Pathol 2004;204:1-10.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Downloads

Published

2019-05-28

Issue

Section

Research Article

How to Cite

1.
Taş D, Köseler A. Diagnostic value of angiopoietin-2 in the differentiation of malignant pleural effusions. J Surg Med [Internet]. 2019 May 28 [cited 2022 Oct. 3];3(5):343-7. Available from: https://jsurgmed.com/article/view/555113