Erdheim-Chester disease (ECD) is a rare histiocytosis, considered to be an inflammatory myeloid neoplasm. Tropism for specific involvements of the disease remains unexplained. Vascular endothelial growth factor-A (VEGF) is implicated in cancer pathophysiology and mutations of the RAS oncogene have been shown to induce the upregulation of VEGF gene expression. We therefore hypothesized that VEGF might play a particular role in ECD pathophysiology.
We conducted a retrospective monocenter study to assess serum VEGF (sVEGF) concentrations and determine whether they were associated with the characteristics of ECD patients, and to determine whether VEGF was expressed by histiocytes.
We evaluated 247 ECD patients, 53.4% of whom had sVEGF levels above the normal range (> 500 pg/mL). Patients with high sVEGF levels more frequently had cardiac and vascular involvement (58.3% vs. 41.4%, p=0.008 and 70.5% vs. 48.3%, p=0.0004, respectively). In treatment-naive patients (n=135), the association of CRP > 5 mg/L and sVEGF > 500 pg/mL was strongly associated with vascular involvement (OR 5.54 [2.39-13.62, p<0.001]), and independently associated with cardiac involvement (OR 3.18 [1.34-7.83, p=0.010]) after adjustment for the presence of the BRAFV600E mutation. Changes in sVEGF concentration on treatment were associated with a response of cardiac involvement on consecutive cardiac MRI scans. All histological samples analyzed (n=24) displayed histiocytes with an intracytoplasmic expression of VEGF, moderate to high in more than 90% of cases. Our study suggests a role for VEGF in cardiac and vascular involvement in ECD.
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