The value of matrix metalloproteinase-9 and vascular endothelial growth factor receptor 1 pathway in diagnosing indeterminate pleural effusion†

Abstract

Our aim was to determine the diagnostic value of the matrix metalloproteinase-9/vascular endothelial grow factor receptor-1 pathway in differentiating pleural effusions (PE) of varying origin. In the last two years, 55 consecutive patients with exudative PE have been enrolled. In all patients, we measured PE levels of vascular endothelial grow factor receptor-1 (VEGFR-1) in soluble form, through enzyme-linked immunosorbent assay (ELISA) (results expressed in pg/ml) and western blot, and of matrix metalloproteinase-9 (MMP-9), through ELISA (results expressed in ng/ml). The values recorded were then statistically compared with the etiologic diagnosis of the PEs. Between the PEs analysed, 40 were found to be malignant and 15 to be benign. VEGFR-1 in soluble form (sVEGFR-1) was significantly higher in malignant than in benign effusions (P < 0.0001), using ELISA; the same was shown by the western blot analysis method. MMP-9 levels results also indicated significantly more malignant than benign effusions (P < 0.0001). VEGFR-1 in soluble form showed a sensitivity and specificity of 92% and 93%, respectively, (cut-off value >852; AUC: 0.9) in predicting the malignant nature of a PE. Sensitivity and specificity of MMP-9 in predicting the malignant nature of a PE were, respectively, 95% and 73% (cut-off value >639; AUC: 0.8). In the pleural fluids, the values of the two markers were significantly related to each other (r = 0.5; P < 0.0001). Eighteen patients with malignancies, diagnosed by pleural biopsy, had negative cytological findings. Of these patients, sixteen (89%) presented elevated levels of both markers. Our data suggest that the VEGFR-1/MMP-9 pathway is significantly increased in malignant-rather than in benign-pleural effusions; thus, the measurement of their levels in the pleural effusion could be useful, throughout the diagnostic work-up, to select which cases would warrant a pleural biopsy.