Objectives: 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.
Methods: 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.
Results: 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.
Conclusions: 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.