Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.

Hemangioblastoma is a highly vascularized, benign tumor in the central nervous system, frequently associated with von Hippel-Lindau (VHL) disease. Hemangioblastoma may cause tumor-associated hemorrhage or exert pressure on nearby structures, leading to life-threatening complications. Although surgic...

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Main Authors: Maya Puttonen, Olli Tynninen, Sami Salmikangas, Tiina Vesterinen, Harri Sihto, Tom Böhling
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0323979
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author Maya Puttonen
Olli Tynninen
Sami Salmikangas
Tiina Vesterinen
Harri Sihto
Tom Böhling
author_facet Maya Puttonen
Olli Tynninen
Sami Salmikangas
Tiina Vesterinen
Harri Sihto
Tom Böhling
author_sort Maya Puttonen
collection DOAJ
description Hemangioblastoma is a highly vascularized, benign tumor in the central nervous system, frequently associated with von Hippel-Lindau (VHL) disease. Hemangioblastoma may cause tumor-associated hemorrhage or exert pressure on nearby structures, leading to life-threatening complications. Although surgical resection is the primary treatment, complete removal is not always feasible. Accordingly, there is a need to explore targeted or anti-angiogenic therapies. The fibroblast growth factor receptor (FGFR) family has roles in tumorigenesis and angiogenesis, making it a potential target in personalized therapy. The distribution and significance of FGFRs in hemangioblastoma have yet to be investigated. We examined 139 formalin-fixed, paraffin-embedded hemangioblastoma samples from 111 patients, including sporadic cases and those associated with VHL disease. Immunohistochemistry revealed positive staining for FGFR2 (95%) and FGFR4 (61%), while FGFR1 (0%) and FGFR3 (12%) were mainly negative. FGFR2 expression was significantly increased in VHL-mutated tumors (75%, p = 0.034) and in male patients (68%, p = 0.020). Tumors located in the cerebrum (n = 6, 5%) had a higher likelihood of positive FGFR4 staining (100%, p = 0.009). Additionally, a larger tumor diameter was associated with a higher likelihood of FGFR4 expression (median 12.0 mm vs 17.5 mm, p = 0.018), suggesting its contribution in tumor growth. Our study revealed the expression of FGFR2 and FGFR4 in a significant number of hemangioblastomas. This finding demonstrates the potential of FGFRs as promising therapeutic targets for patients with hemangioblastoma.
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spelling doaj-art-708ef61d1ec74a1f9e2a0b555b85114d2025-08-20T03:08:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01205e032397910.1371/journal.pone.0323979Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.Maya PuttonenOlli TynninenSami SalmikangasTiina VesterinenHarri SihtoTom BöhlingHemangioblastoma is a highly vascularized, benign tumor in the central nervous system, frequently associated with von Hippel-Lindau (VHL) disease. Hemangioblastoma may cause tumor-associated hemorrhage or exert pressure on nearby structures, leading to life-threatening complications. Although surgical resection is the primary treatment, complete removal is not always feasible. Accordingly, there is a need to explore targeted or anti-angiogenic therapies. The fibroblast growth factor receptor (FGFR) family has roles in tumorigenesis and angiogenesis, making it a potential target in personalized therapy. The distribution and significance of FGFRs in hemangioblastoma have yet to be investigated. We examined 139 formalin-fixed, paraffin-embedded hemangioblastoma samples from 111 patients, including sporadic cases and those associated with VHL disease. Immunohistochemistry revealed positive staining for FGFR2 (95%) and FGFR4 (61%), while FGFR1 (0%) and FGFR3 (12%) were mainly negative. FGFR2 expression was significantly increased in VHL-mutated tumors (75%, p = 0.034) and in male patients (68%, p = 0.020). Tumors located in the cerebrum (n = 6, 5%) had a higher likelihood of positive FGFR4 staining (100%, p = 0.009). Additionally, a larger tumor diameter was associated with a higher likelihood of FGFR4 expression (median 12.0 mm vs 17.5 mm, p = 0.018), suggesting its contribution in tumor growth. Our study revealed the expression of FGFR2 and FGFR4 in a significant number of hemangioblastomas. This finding demonstrates the potential of FGFRs as promising therapeutic targets for patients with hemangioblastoma.https://doi.org/10.1371/journal.pone.0323979
spellingShingle Maya Puttonen
Olli Tynninen
Sami Salmikangas
Tiina Vesterinen
Harri Sihto
Tom Böhling
Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.
PLoS ONE
title Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.
title_full Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.
title_fullStr Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.
title_full_unstemmed Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.
title_short Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.
title_sort fibroblast growth factor receptor expression in hemangioblastomas a novel therapeutic target
url https://doi.org/10.1371/journal.pone.0323979
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AT samisalmikangas fibroblastgrowthfactorreceptorexpressioninhemangioblastomasanoveltherapeutictarget
AT tiinavesterinen fibroblastgrowthfactorreceptorexpressioninhemangioblastomasanoveltherapeutictarget
AT harrisihto fibroblastgrowthfactorreceptorexpressioninhemangioblastomasanoveltherapeutictarget
AT tombohling fibroblastgrowthfactorreceptorexpressioninhemangioblastomasanoveltherapeutictarget