Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications

Abstract

Our goal was to determine the role of vascular endothelial growth factor (VEGF) in diagnosing of pleural effusion (PE) in order to select patients deserving of more aggressive procedures. Seventy-nine consecutive patients with undiagnosed unilateral PE were enrolled. Pleural VEGF levels, measured using enzyme-linked immunosorbent assay (ELISA), were correlated to etiology of PEs and other markers (protein, lactic dehydrogenase, amylase, glucose). The median level of VEGF in exudates (n=65) was significantly higher than that in transudates (P=0.0001) and among exudates, it was significantly higher in malignant (n=49) than that in benign exudates (P=0.005). No significant differences were observed between malignant effusions due to lung cancer (n=11) and other malignant effusions [mesothelioma (n=13) and/or extra-thoracic cancer]. Among all variables evaluated, logistic regression found that only VEGF was significantly correlated with the presence of malignant disease (P=0.002). Analysis of the receiver operating characterists (ROC) curves showed that the areas under the curve of VEGF were significantly larger than that of amylase (P=0.02), glucose (P=0.01), lactic dehydrogenase (P=0.001) and protein (P=0.01). VEGF increased the diagnostic rate of cytological examination by 24%. VEGF may represent a helpful adjunct to conventional diagnostic tools in ruling out malignancy as a probable diagnosis, thus guiding the selection of patients who might benefit from further invasive procedures.

Vascular endothelial growth factor and protein level in pleural effusion for differentiating malignant from benign pleural effusion

“…VEGF was used as a biomarker in the present study (optimal cutoff value=214 pg/ml). Duysinx et al (26) suggested that the optimal value of VEGF for differentiating MPE from BPE is 382 pg/ml and Fiorelli et al (27) demonstrated that sensitivity and specificity were 63 and 83%, respectively, when VEGF is >652 pg/ml. These cutoff values may differ from that of the present study due to the use of different experimental designs and sample sizes.…”

Application of MMP-7 and MMP-10 in Assisting the Diagnosis of Malignant Pleural Effusion

“…The practical use of a tumor marker is linked to its capacity to detect occult disease at a still treatable stage or to reliably indentify occult metastases (Fiorelli et al, 2011). In ROC analysis MMP-7 levels provide a sensitivity and specificity value of 82.8% and 73.9%, and MMP-10 levels provide a sensitivity and specificity value of 86.2% and 64.1%, respectively.…”

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).…”