Diagnostic value of serum VEGF-D in consecutive patients with lymphangioleiomyomatosis

Background: Serum levels of vascular endothelial growth factor-D (VEGF-D) are increased in patients with lymphangioleiomyomatosis (LAM). Objective: To explore the value of measurement of serum level of VEGF-D for the diagnosis of LAM. Methods: Serum levels of VEGF-D were measured prospectively in 45 patients with LAM (mean age, 48±13 years), 13 healthy controls, and 23 patients with multiple cystic lung diseases other than LAM. Results: Serum VEGF-D levels were significantly higher in patients with LAM (mean, 1856±1742 pg/mL) than in patients with other lung diseases (410±173 pg/mL, p<0.01) or healthy individuals (230±69 pg/mL, p<0.0001). VEGF-D was elevated (860 pg/mL) in only one patient with Birt-Hogg-Dubé disease with the mutation PQ385X in the FLCN gene, with LAM ruled out by lung biopsy. Using 800 pg/mL as a threshold, the specificity of VEGF-D was 98% but sensitivity was only 76%. VEGF-D in LAM was >800 pg/mL in 5/7 transplanted patients, in 6/6 patients receiving sirolimus, and in 4/4 patients treated with doxycycline. VEGF-D levels did not correlate with any pulmonary function parameter. Conclusion: Serum VEGF-D levels greater than 800 pg/mL contributes to the diagnosis of LAM with false positive only rarely encountered (as in Birt Hogg Dubé disease). Serum VEGF-D level may remain elevated in transplanted patients and those receiving medical therapy. Financial support: CNMR and FP7 of the European Commission.