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 ∼ 1412.6) vs. 295.9 pg/mL
(262.6 ∼ 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.
