Vascular endothelial growth factor in pleural effusions of different origin

Abstract

This study aimed to determine the diagnostic relevance of vascular endothelial growth factor (VEGF) in the pleural fluid and serum of patients with pleural effusions of different aetiology.VEGF was quantified in the pleural effusion fluid and serum of 96 patients with malignancies (58 lung cancers (CA) and 38 tumours with secondaries to the lung (TM)), 45 with congestive heart failure (CHF), 28 with tuberculosis (TB), 45 with acute infections (INF), and in the serum of 20 healthy controls.VEGF pleural effusion concentrations were significantly different in the main diagnostic groups. VEGF was higher in effusions of patients with malignancies (CA as well as TM) in comparison with INF, TB or CHF. In serum, however, high VEGF concentrations indicated CA, TM or INF, but not TB or CHF. Despite significant differences of VEGF levels in different patient groups, receiver-operating characteristic analysis revealed insufficient diagnostic value of VEGF for differential diagnosis of pleural effusions.In conclusion, vascular endothelial growth factor serum concentration is highly suggestive of the presence of lung disease in general, except for tuberculosis. In effusion fluid, the presence of vascular endothelial growth factor clearly indicates inflammatory or malignant origin. However, for diagnostic use, additional parameters besides vascular endothelial growth factor are mandatory.

Clinical utility of vascular endothelial growth factor in diagnosing malignant pleural effusions

“…As for the accumulation of VEGF in PF, not only mesothelial cells, infiltrating inflammatory cells and in malignant PE, cancer cells but also adjacent epithelial cells, type II alveolar cells, alveolar macrophages, infiltrating neutrophils and eosinophils of the lung may contribute to it [17]. With respect to no statistical difference in the ratio of PF VEGF to serum VEGF between groups, that might be resulted from the parallel elevation of VEGF levels of PF and serum in malignancy.…”

“…For combination tests, there are also a tradeoff between the sensitivity and specificity, where the likelihood ratio and Youden Index may be used for overall assessment of test strategies. For cascade connection and parallel operation of PF VEGF test and serum VEGF test, the former had the most predominant positive likelihood ratio (17), whereas the latter possessed the most superior Youden Index (0.67) and negative likelihood ratio (0.22). These different test strategies may be selected according to practical purposes.…”

Prognostic Values of VEGF and Endostatin with Malignant Pleural Effusions in Patients with Lung Cancer

“…Different authors have highlighted the role played by VEGF in the accumulation of exudative PE, especially that of MPE associated with lung cancer (Yanagawa et al, 1999). A few studies (Sack et al, 2005;Zhang et al, 2012;Zhou et al, 2009;Koniari et al, 2011;Yanagawa et al, 1999;Ziora et al, 2002;Fiorelli et al, 2011) have suggested that high VEGF levels in both serum and PE might be considered predictive of malignancy. In agreement with previous reports, the current study found that VEGF levels in PE and serum are significantly higher in malignant than in benign effusions.…”

“…Endostatin is one of a number of endogenously generated antiangiogenic protein fragments that have been shown to have antitumor activity in murine models (Skovseth et al, 2005). Although serum levels of endostatin have extensively been studied in patients with malignant diseases, only a few studies evaluated endostatin levels in PE (Sumi et al, 2003;Ruiz et al, 2005;Sack et al, 2005;Zhang et al, 2012;Koniari et al, 2011;Hsu et al, 2009;Yanagawa et al, 1999;Ziora et al, 2002;Fiorelli et al, 2011;. Previous studies reported that in comparison with either VEGF or endostatin determination in serum or pleural fluid, the combined detection of two factors improved the diagnostic sensitivity and accuracy (Zhang et al, 2012;Zhou et al, 2009).…”

“…Previous research has investigated pleural angiogenic factors and angiogenesis inhibitors determinations play a role in the diagnosis (Sack et al, 2005;Zhou et al, 2009;Koniari et al, 2011;Zhang et al, 2012), and VEGF has been reported to be correlated with a poor prognosis (Hsu et al, 2009). However, these two kinds of important factors have not yet been quantified simultaneously to determine their potential prognostic uses.…”