Abstract

Lymphangioleiomyiomatosis (LAM) is a rare cystic disease affecting primarily women. It could develop in a sporadic form (S-LAM) and in women with tuberous sclerosis complex (TSC-LAM). Serum level of vascular endothelial growth factor D (VEGF-D) higher than 800 pg/mL in presence of typical cystic changes seen at chest CT scan is diagnostic. We assessed serum levels of VEGF-D, VEGF-C, MMP-2 and MMP-7 in a cohort of patients affected by S-LAM and TSC with and without LAM. Our aim was to confirm the diagnostic value of VEGF-D in LAM patients and to explore its value in TSC patients. We also explored the distribution of the others biomarkers. Serum level of VEGF-D and C, MMP-2 and -7 were quantified by ELISA assays for 52 adult women with S-LAM and TSC and for 16 healthy controls. ROC curves were built to explore diagnostic potential of every biomarker. VEGF-D, MMP-2 and MMP7 were higher in patients with LAM than in patients without; there was no difference in VEGF-C levels in groups. All controls had a VEGF-D less than 800 pg/mL; sensitivity (Se) and specificity (Sp) of the biomarkers for the diagnosis of LAM in the whole cohort and in TSC patients are reported in Figure 1.

The diagnostic value of VEGF-D in S-LAM was confirmed. Sp of VEGF-D in TSC patients was low probably due to lymphatic involvement linked to TSC. MMP-2 and MMP 7 are promising biomarkers for LAM.