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

Our plain-English summary of Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications, by A. Fiorelli, G. Vicidomini, M. Di Domenico, et al (Interactive Cardiovascular and Thoracic Surgery, 2011).

The study

• Authors: A. Fiorelli, G. Vicidomini, M. Di Domenico, F. Napolitano, G. Messina, F. Morgillo, F. Ciardiello, M. Santini
• Journal: Interactive Cardiovascular and Thoracic Surgery
• Published: 2011;12(3):420-4
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This study from the Second University of Naples, Italy, measured vascular endothelial growth factor (VEGF), a protein involved in blood-vessel growth, in the chest fluid (pleural effusion) of 79 consecutive patients. Each had an undiagnosed effusion on one side and was enrolled from January 2006 to January 2009. Forty-nine had malignant effusions, 13 of them mesothelioma. Asbestos exposure was not examined. Median VEGF was 654 in exudates versus 315 in transudates. Among exudates, it was 753 in malignant versus 469 in benign effusions. Levels did not differ significantly between lung cancer and other malignant effusions. Of the fluid markers tested, only VEGF was significantly associated with malignancy, and it had the largest area under the ROC curve (0.801). Above a cut-off of 652 pg/ml, VEGF had 63% sensitivity and 83% specificity. Cytology found cancer in 29 of 49 malignant cases (59%). Combining cytology with VEGF raised detection to 83%. Five benign effusions also had high VEGF. The authors concluded VEGF may help conventional tests select patients for further invasive procedures, but should not replace tissue or cell diagnosis.

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: Diagnostic study at a single institution (published as an institutional report). VEGF was measured by ELISA in pleural fluid from consecutive patients, and laboratory staff were blinded to clinical data. Results were compared with final diagnosis and with routine fluid markers.
• Who was studied: 79 consecutive patients (43 male, 36 female; median age 68, range 23 to 87) with undiagnosed pleural effusion on one side, enrolled January 2006 to January 2009 at the Second University of Naples, Italy. Patients with effusions on both sides were excluded. 14 had transudates and 65 had exudates. Of the exudates, 16 were benign and 49 were malignant: 11 lung, 14 breast, 7 gastro-intestinal, 1 ovary, 1 leukemia, 1 laryngeal, 1 kidney and 13 mesothelioma.
• Exposure: Not an asbestos exposure study. No fiber types or occupational exposures were studied. The measure examined was VEGF level in pleural fluid, compared with protein, lactic dehydrogenase (LDH), amylase and glucose.
• Main results:
  • Median pleural VEGF was 654 (interquartile range 426 to 980) in patients with exudates. This was significantly higher than 315 (218 to 386) in patients with transudates (P=0.0001).
  • Among exudates, median VEGF was 753 (458 to 1200) in malignant effusions (n=49). This was significantly higher than 469 (330 to 653) in benign effusions (P=0.005).
  • There were no significant differences in VEGF between effusions due to lung cancer (n=11) and other malignant effusions (mesothelioma, n=13, and/or extra-thoracic cancer).
  • In logistic regression, only VEGF was significantly associated with malignant disease: odds ratio 1.0032, 95% CI 1.0012 to 1.0052, P=0.002. Amylase, glucose, LDH and protein were not.
  • The area under the ROC curve for VEGF was 0.801 (95% CI 0.696 to 0.882). This was significantly larger than for amylase (0.626, P=0.02), glucose (0.607, P=0.01), LDH (0.537, P=0.001) and protein (0.633, P=0.01).
  • At a cut-off above 652 pg/ml, VEGF had 63% sensitivity, 83% specificity, 86% positive predictive value and 58% negative predictive value for malignancy.
  • Cytology diagnosed malignancy in 59% of malignant cases (29 of 49). The remaining 20 were diagnosed by thoracoscopic biopsy. Twelve cytology-negative malignant patients had VEGF above 652, so combining cytology with VEGF raised detection to 83% versus 59%, a 24% increase.
  • Logistic regression found no significant relationship between VEGF levels and the presence of cancer cells in the effusions.
  • Five patients with benign effusions had VEGF above 652: one transudate, three empyema and one tuberculosis.
• The authors' conclusion: The authors concluded that pleural VEGF levels were considerably higher in malignant effusions than in other groups. They wrote that VEGF may be a helpful adjunct to conventional diagnostic tools in ruling out malignancy as a probable diagnosis, helping select patients for further invasive procedures. They stated it should not substitute for cytological or histological demonstration of malignancy.
• Limitations the authors state:
  • Eight of the 20 cytology-negative malignant patients had low VEGF (below 652), so VEGF missed some cancers.
  • The authors stated that routine or indiscriminate VEGF testing in all effusions is probably not cost-effective and cannot be recommended.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Differential Diagnosis, Pleural Effusion, Etiology, Exudate, Lung Cancer, Mesothelioma.

Related studies

• Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma — A. Yasumitsu, C. Tabata, et al. (2010)
• Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma — N. Fujimoto, K. Gemba, et al. (2011)
• Novel orthotopic implantation model of human malignant pleural mesothelioma (EHMES-10 cells) highly expressing vascular endothelial growth factor and its receptor — E. Nakataki, S. Yano, et al. (2006)
• Significance of secretory leukocyte peptidase inhibitor in pleural fluid for the diagnosis of benign asbestos pleural effusion — T. Kishimoto, Y. Kojima, et al. (2021)
• Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma — L. Strizzi, A. Catalano, et al. (2001)
• Diagnostic usefulness of tumour marker levels in pleural effusions of malignant and benign origin — F. Kuralay, Z. Tokgöz, et al. (2000)

Browse more research in Interactive Cardiovascular and Thoracic Surgery, or return to medical research.