Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease
Anais Roeser,
Marine Bravetti,
Lida Dong,
Levi-Dan Azoulay,
Frederic Charlotte,
Makoto Miyara,
Pascale Ghillani-Dalbin,
Jean-Francois Emile,
Fadwa El Kouari,
Hamza Ouni,
Jean-Marc Lacorte,
Isabelle Brocheriou,
Zahir Amoura,
Fleur Cohen-Aubart,
Julien Haroche
Affiliations
Anais Roeser
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Service de Medecine Interne 2, Centre National de Reference des Histiocytoses, Paris-75013
Marine Bravetti
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Service de Radiologie Cardiovasculaire et Interventionnelle, Paris-75013
Lida Dong
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Service d’Anatomie et Cytologie Pathologiques, Paris-75013
Levi-Dan Azoulay
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Service de Medecine Interne 2, Centre National de Reference des Histiocytoses, Paris-75013
Frederic Charlotte
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Service d’Anatomie et Cytologie Pathologiques, Paris-75013
Makoto Miyara
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Departement d’Immunochimie, Paris-75013
Pascale Ghillani-Dalbin
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Departement d’Immunochimie, Paris-75013
Jean-Francois Emile
EA4340, Universite Versailles-Saint Quentin, Assistance Publique Hopitaux de Paris, Hopital Ambroise Pare, Departement de Pathologie, Boulogne-92100
Fadwa El Kouari
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Unite fonctionnelle de production des medicaments et des anticancereux injectables, Hopital Pitie-Salpetriere, Paris-75013
Hamza Ouni
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Service de Biochimie Endocrinienne et Oncologique, Hopital Pitie-Salpetriere, Paris-75013
Jean-Marc Lacorte
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Service de Biochimie Endocrinienne et Oncologique, Hopital Pitie-Salpetriere, Paris-75013
Isabelle Brocheriou
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Service d’Anatomie et Cytologie Pathologiques, Paris-75013
Zahir Amoura
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Service de Medecine Interne 2, Centre National de Reference des Histiocytoses, Paris-75013
Fleur Cohen-Aubart
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Service de Medecine Interne 2, Centre National de Reference des Histiocytoses, Paris-75013
Julien Haroche
Sorbonne Universite, Assistance Publique Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Service de Medecine Interne 2, Centre National de Reference des Histiocytoses, Paris-75013
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 upregulation of VEGF gene expression. We therefore hypothesized that VEGF might play a particular role in ECD pathophysiology. We conducted a retrospective, single-center 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-naïve patients (n=135), the association of C-reactive protein >5 mg/L and sVEGF >500 pg/mL was strongly associated with vascular involvement (odds ratio=5.54 [95% confidence interval: 2.39-13.62], P<0.001), and independently associated with cardiac involvement (odds ratio=3.18 [95% confidence interval: 1.34-7.83], P=0.010) after adjustment for the presence of the BRAF V600E mutation. Changes in sVEGF concentration on treatment were associated with a response of cardiac involvement on consecutive cardiac magnetic resonance images. All histological samples analyzed (n=24) displayed histiocytes with intracytoplasmic expression of VEGF, which was moderate to high in more than 90% of cases. Our study suggests a role for VEGF in cardiac and vascular involvement in ECD.