Background: Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease characterized by an abnormal proliferation of smooth muscle-like cells (LAM cells) in the lung and along the axial lymphatics. LAM demonstrates a heterogeneous clinical course, but there is no serum surrogate marker available for assessing the disease severity or predicting the disease progression. Since the authors have recently demonstrated the extensive LAM-associated lymphangiogenesis and its potential role in progression and metastasis of LAM cells, they hypothesized that serum levels of lymphangiogenic growth factors might be increased in LAM and become a surrogate marker for disease severity.
Methods and results: VEGF-A, VEGF-C, and VEGF-D in serum of 44 patients with LAM were measured by enzyme-linked immunosorbant assay. Only VEGF-D was significantly increased in LAM patients as compared with age- and gender-matched healthy volunteers (n=24) (LAM vs. control, geometric mean 95% CI; 1069.3 pg/mL (809.4 approximately 1412.6) vs. 295.9 pg/mL (262.6 approximately 333.5), p<0.0001). Serum VEGF-D levels negatively correlated with variables of pulmonary function tests, FEV1/FVC (forced expiratory volume in one second/forced vital capacity) (r=-0.365, p<0.05) and %DLco/VA (the percentage of diffusing capacity for carbon monoxide/alveolar volume to the predicted value) (r=-0.560, p<0.001). As expected, the group who received hormone therapy showed more deteriorated pulmonary function with higher serum VEGF-D levels than the group who was just observed without hormone therapy. Immunohistochemical examination of lung specimens demonstrated the positive immunoreactivity of LAM cells for VEGF-D.
Conclusion: Serum VEGF-D levels may be a valuable surrogate marker for evaluating the disease severity in LAM.