Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease

Abstract

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

Cardiovascular manifestations of Erdheim–Chester disease: A narrative review with two cases

“…High levels are significantly associated with cardiovascular involvement and improvement in VEGF mirrors cardiovascular response to treatment and survival. 7 VEGF may serve as a method of detection and monitoring of cardiovascular manifestations in ECD.…”

“…5 Mutations in RAS genes, specifically KRAS and NRAS, are known to cause ECD and are associated with upregulation of vascular endothelial growth factor (VEGF) expression. 7 Roeser et al found that high serum VEGF levels (> 500 pg/mL) were associated with cardiovascular involvement. 8 They noted 68.8% of their patients with high VEGF had vascular involvement ('coated' aorta, mesenteric arteries, renal arteries) compared to 48.6% with low VEGF (p = 0.001).…”