Serum vascular endothelial growth factor-D levels in patients with lymphangioleiomyomatosis reflect lymphatic involvement.
BACKGROUND
Lymphangioleiomyomatosis (LAM) is a rare multisystem disorder affecting primarily women of child-bearing age, and characterized by cystic lung destruction, tumors of the kidney (angiomyolipomas [AMLs]), and involvement of the axial lymphatics (lymphangioleiomyomas). Patients with LAM experience loss of pulmonary function attributed to the proliferation of abnormal-appearing smooth muscle-like cells (LAM cells). It is possible to group the LAM population by the presence or absence of extrapulmonary involvement (eg, AMLs, lymphangioleiomyomas, chylous effusions). Serum vascular endothelial growth factor (VEGF)-D, a lymphangiogenic factor, is higher in LAM patients than in healthy volunteers and has been proposed as a tool in the differential diagnosis of cystic lung disease. We assessed serum VEGF-D concentrations in relationship to clinical phenotype in LAM patients.


METHODS
Serum VEGF-D levels were quantified by enzyme immunosorbent assay for 111 patients with LAM and 40 healthy volunteers. VEGF-D levels in patients with pulmonary LAM, with or without extrapulmonary manifestations, were compared to those of healthy volunteers.


RESULTS
Serum VEGF-D levels were greater in patients with LAM compared to those of healthy volunteers (p < 0.001). However, when patient samples were grouped based on the extent of lymphatic extrapulmonary involvement (eg, lymphangioleiomyomas and adenopathy), the statistical difference was maintained only for patients with LAM with lymphatic involvement (p < 0.001), not for those patients whose disease was restricted to the lung. Serum VEGF-D levels are a good biomarker for lymphatic involvement (area under the curve [AUC], 0.845; p < 0.0001), and a fair predictor for LAM disease (AUC, 0.751; p < 0.0001). Serum levels correlated to CT scan grade (p = 0.033).


CONCLUSIONS
Serum VEGF-D concentration is a measure of lymphatic involvement in patients with LAM.
Glasgow
Connie G
CG
Translational Medicine Branch, National Institutes of Health, Bethesda, MD.
Avila
Nilo A
NA
Diagnostic Radiology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD.
Lin
Jing-Ping
JP
Office of Biostatistics Research, Division of Prevention and Population Science, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Stylianou
Mario P
MP
Office of Biostatistics Research, Division of Prevention and Population Science, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Moss
Joel
J
Translational Medicine Branch, National Institutes of Health, Bethesda, MD. Electronic address: mossj@nhlbi.nih.gov.
D019540:Area Under Curve; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D016015:Logistic Models; D018192:Lymphangioleiomyomatosis / Q000097:blood* / Q000473:pathology*; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D042643:Vascular Endothelial Growth Factor D / Q000097:blood*; D014797:Vital Capacity
D042643:Vascular Endothelial Growth Factor D