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Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease
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 b...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Fondazione Ferrata Storti
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890031/ https://www.ncbi.nlm.nih.gov/pubmed/36005561 http://dx.doi.org/10.3324/haematol.2022.280755 |
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author | Roeser, Anaïs Bravetti, Marine Dong, Lida Azoulay, Levi-Dan Charlotte, Frederic Miyara, Makoto Ghillani-Dalbin, Pascale Emile, Jean-François El Kouari, Fadwa Ouni, Hamza Lacorte, Jean-Marc Brocheriou, Isabelle Amoura, Zahir Cohen-Aubart, Fleur Haroche, Julien |
author_facet | Roeser, Anaïs Bravetti, Marine Dong, Lida Azoulay, Levi-Dan Charlotte, Frederic Miyara, Makoto Ghillani-Dalbin, Pascale Emile, Jean-François El Kouari, Fadwa Ouni, Hamza Lacorte, Jean-Marc Brocheriou, Isabelle Amoura, Zahir Cohen-Aubart, Fleur Haroche, Julien |
author_sort | Roeser, Anaïs |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9890031 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Fondazione Ferrata Storti |
record_format | MEDLINE/PubMed |
spelling | pubmed-98900312023-02-13 Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease Roeser, Anaïs Bravetti, Marine Dong, Lida Azoulay, Levi-Dan Charlotte, Frederic Miyara, Makoto Ghillani-Dalbin, Pascale Emile, Jean-François El Kouari, Fadwa Ouni, Hamza Lacorte, Jean-Marc Brocheriou, Isabelle Amoura, Zahir Cohen-Aubart, Fleur Haroche, Julien Haematologica Article - Inflammatory Myeloid Neoplasm 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. Fondazione Ferrata Storti 2022-08-25 /pmc/articles/PMC9890031/ /pubmed/36005561 http://dx.doi.org/10.3324/haematol.2022.280755 Text en Copyright© 2023 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Article - Inflammatory Myeloid Neoplasm Roeser, Anaïs Bravetti, Marine Dong, Lida Azoulay, Levi-Dan Charlotte, Frederic Miyara, Makoto Ghillani-Dalbin, Pascale Emile, Jean-François El Kouari, Fadwa Ouni, Hamza Lacorte, Jean-Marc Brocheriou, Isabelle Amoura, Zahir Cohen-Aubart, Fleur Haroche, Julien Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease |
title | Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease |
title_full | Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease |
title_fullStr | Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease |
title_full_unstemmed | Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease |
title_short | Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease |
title_sort | serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in erdheim-chester disease |
topic | Article - Inflammatory Myeloid Neoplasm |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890031/ https://www.ncbi.nlm.nih.gov/pubmed/36005561 http://dx.doi.org/10.3324/haematol.2022.280755 |
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