The role of vascular endothelial growth factor-D in diagnosis of lymphangioleiomyomatosis (LAM)

Abstract

Definite diagnosis of lymphangioleiomyomatosis (LAM) depends on either transbronchial lung biopsy or video-assisted thoracic surgery, unless there is a history of chylothorax, kidney angiomyolipoma (AML), or tuberous sclerosis complex (TSC). Vascular endothelial growth factor-D (VEGF-D) was recently considered as a novel diagnostic marker for LAM. Herein, we evaluated diagnostic value of serum VEGF-D in LAM patients. Serum samples were obtained from 78 cases of LAM (50 definite and 28 probable LAM based on European Respiratory Society guidelines), and 40 healthy female volunteers. VEGF-D was measured using enzyme-linked immunosorbant assay according to product instruction (R&D). Serum VEGF-D was significantly increased in definite LAM group, compared with that of health control (median: 3841.9pg/mL vs 405.5pg/mL respectively, p<0.001). The optimal cut-off point for definite LAM diagnosis was 850.7pg/mL. In probable LAM group, the majority of patients (92.9%) had serum VEGF-D level over 850.7pg/mL. The serum levels of VEGF-D in LAM patients with pulmonary cystic lesions only were lower than that in patients with any of evidences of AML, chylous effusions, adenopathy, lymphangioleiomyomas, or TSC, but higher than that in the health control. In addition, VEGF-D levels were correlated with disease severity measured as LAM CT grade, and presentations of chylous effusions and/or lymphatic involvement (p<0.05). Serum VEGF-D should be added to the current diagnosis algorithm to enhance definitive diagnosis for LAM.