Diagnostic value of interleukine-6, transforming growth factor-beta 1 and vascular endothelial growth factor in malignant pleural effusions

Summary 

Study objectives

We evaluate the accuracy of pleural interleukine-6 (IL-6), transforming growth factor-beta 1 (TGF-β1), and vascular endothelial growth factor (VEGF) levels for differentiating benign from malignant pleural exudates.

Patients and methods

Levels of IL-6, TGF-β1, and VEGF were measured by ELISA in 103 patients with non neutrophilic (<50%) exudative pleurisy including both benign and malignant effusions. Pleurisies were splitted into benign and malignant according to the pathological diagnosis.

Results

Thirty-nine benign (seven infections; 32 inflammatory diseases) and 64 malignant (34 extrathoracic tumors; 25 lung cancers; five mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Pleural reticulo-monocyte count, protein Light's ratio and lactic dehydrogenase Light's ratio were significantly higher in malignant than in benign effusions (p<0.05, p<0.001 and p<0.001, respectively). The median (range) level of VEGF was significantly higher in malignant than in benign effusions (664.50pg/ml [10–40,143] vs 349pg/ml [10–8888]) (p<0.05). VEGF levels correlated with pleural LDH (r=0.41, p<0.0001), glucose (r=−0.30, p<0.01) and red cell count (r=0.57, p<0.0001).

No significant difference was found between malignant and benign effusions with respect to IL-6 (26.8ng/ml [1.8–421] vs 18.4ng/ml [0.45–400], respectively) and TGF-β1 (1079pg/ml [18–6206] vs 1123pg/ml [34–5447]) levels.

ROC analysis between benign and malignant pleurisies for VEGF showed an area under the curve of 619 (p=0.03) with a value of 382pg/ml as the best threshold for distinguishing benign from malignant effusions.

Conclusions

Malignant effusions may enhance the release of VEGF in pleural space and its measurement may help in the diagnosis of malignant effusion.

Keywords: Pleural cytokines, Pleural effusion, Cancer, Lymphocyte effusion, Exudate, VEGF