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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 <jats:italic>VHL<\/jats:italic>-mutated tumors (75%, <jats:italic>p<\/jats:italic>\u2009=\u20090.034) and in male patients (68%, <jats:italic>p<\/jats:italic>\u2009=\u20090.020). Tumors located in the cerebrum (<jats:italic>n<\/jats:italic>\u2009=\u20096, 5%) had a higher likelihood of positive FGFR4 staining (100%, <jats:italic>p<\/jats:italic>\u2009=\u20090.009). Additionally, a larger tumor diameter was associated with a higher likelihood of FGFR4 expression (median 12.0\u2009mm vs 17.5\u2009mm, <jats:italic>p<\/jats:italic>\u2009=\u20090.018), 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.<\/jats:p>","DOI":"10.1371\/journal.pone.0323979","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T20:01:41Z","timestamp":1747771301000},"page":"e0323979","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic 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classification of tumours","author":"Central Nervous System Tumours","year":"2021"},{"key":"pone.0323979.ref002","doi-asserted-by":"crossref","DOI":"10.1016\/j.wneu.2017.11.173","article-title":"Hemangioblastomas of the Posterior Cranial Fossa in adults: demographics, clinical, morphologic, pathologic, surgical features, and outcomes. a systematic review","volume":"110","author":"M Kuharic","year":"2018","journal-title":"World Neurosurg"},{"issue":"6161","key":"pone.0323979.ref003","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/332268a0","article-title":"Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma","volume":"332","author":"BR Seizinger","year":"1988","journal-title":"Nature"},{"issue":"8","key":"pone.0323979.ref004","doi-asserted-by":"crossref","first-page":"104538","DOI":"10.1016\/j.ejmg.2022.104538","article-title":"von Hippel-Lindau disease: Updated guideline for diagnosis and surveillance","volume":"65","author":"M Louise M Binderup","year":"2022","journal-title":"Eur J Med Genet"},{"key":"pone.0323979.ref005","article-title":"Symptoms, diagnosis and treatment of hemangioblastoma dissemination","author":"M Halim","year":"2019","journal-title":"OA J Radiol"},{"issue":"3","key":"pone.0323979.ref006","doi-asserted-by":"crossref","first-page":"37","DOI":"10.15586\/jkcvhl.2017.90","article-title":"Management strategies and outcomes for VHL-related Craniospinal Hemangioblastomas","volume":"4","author":"C Ordookhanian","year":"2017","journal-title":"J Kidney Cancer VHL"},{"issue":"7","key":"pone.0323979.ref007","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.3390\/cancers16071261","article-title":"Predictors of progression in a series of 81 adult patients surgically managed for an intracranial hemangioblastoma: implications for the postoperative follow-up","volume":"16","author":"E Garrido","year":"2024","journal-title":"Cancers 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Javle","year":"2023","journal-title":"Oncologist"},{"issue":"3","key":"pone.0323979.ref014","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1158\/2159-8290.CD-12-0362","article-title":"Fibroblast growth factor receptor inhibitors as a cancer treatment: from a biologic rationale to medical perspectives","volume":"3","author":"MV Dieci","year":"2013","journal-title":"Cancer Discov"},{"issue":"2","key":"pone.0323979.ref015","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.cytogfr.2005.01.007","article-title":"Mechanisms underlying differential responses to FGF signaling","volume":"16","author":"L Dailey","year":"2005","journal-title":"Cytokine Growth Factor Rev"},{"issue":"7","key":"pone.0323979.ref016","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/35017054","article-title":"Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein","volume":"2","author":"M Ohh","year":"2000","journal-title":"Nat Cell Biol"},{"issue":"3","key":"pone.0323979.ref017","first-page":"253","article-title":"Understanding and targeting resistance to anti-angiogenic therapies","volume":"4","author":"JM Clarke","year":"2013","journal-title":"J Gastrointest Oncol"},{"issue":"1","key":"pone.0323979.ref018","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11060-005-3279-0","article-title":"Hypoxia inducible factor 1-alpha regulates of platelet derived growth factor-B in human glioblastoma cells","volume":"76","author":"D Yoshida","year":"2006","journal-title":"J Neurooncol"},{"issue":"40","key":"pone.0323979.ref019","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1214019109","article-title":"Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells","volume":"109","author":"L Schito","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pone.0323979.ref020","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1128\/MCB.16.9.4604","article-title":"Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1","volume":"16","author":"JA Forsythe","year":"1996","journal-title":"Mol Cell Biol"},{"issue":"13","key":"pone.0323979.ref021","doi-asserted-by":"crossref","first-page":"5680","DOI":"10.1073\/pnas.88.13.5680","article-title":"Hypoxia-inducible nuclear factors bind to an enhancer element located 3\u2019 to the human erythropoietin gene","volume":"88","author":"GL Semenza","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pone.0323979.ref022","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1097\/00062752-199805000-00003","article-title":"Regulation of expression of the erythropoietin gene","volume":"5","author":"P Maxwell","year":"1998","journal-title":"Curr Opin Hematol"},{"issue":"6","key":"pone.0323979.ref023","first-page":"1358","article-title":"Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas","volume":"55","author":"S Wizigmann-Voos","year":"1995","journal-title":"Cancer Res"},{"issue":"12","key":"pone.0323979.ref024","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1586\/14737140.2015.1110488","article-title":"Targeting fibroblast growth factor receptor (FGFR) pathway in renal cell carcinoma","volume":"15","author":"F Massari","year":"2015","journal-title":"Expert Rev Anticancer Ther"},{"issue":"5","key":"pone.0323979.ref025","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3390\/cells8050455","article-title":"Cross-talk between fibroblast growth factor receptors and other cell surface proteins","volume":"8","author":"M Latko","year":"2019","journal-title":"Cells"},{"issue":"4","key":"pone.0323979.ref026","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.ccr.2005.09.005","article-title":"Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors","volume":"8","author":"O Casanovas","year":"2005","journal-title":"Cancer Cell"},{"issue":"12","key":"pone.0323979.ref027","doi-asserted-by":"crossref","first-page":"4649","DOI":"10.1158\/0008-5472.CAN-07-6003","article-title":"Endothelial function of von Hippel-Lindau tumor suppressor gene: control of fibroblast growth factor receptor signaling","volume":"68","author":"KJ Champion","year":"2008","journal-title":"Cancer Res"},{"issue":"17","key":"pone.0323979.ref028","doi-asserted-by":"crossref","first-page":"12069","DOI":"10.1074\/jbc.M511621200","article-title":"Endocytic function of von Hippel-Lindau tumor suppressor protein regulates surface localization of fibroblast growth factor receptor 1 and cell motility","volume":"281","author":"T Hsu","year":"2006","journal-title":"J Biol Chem"},{"issue":"12","key":"pone.0323979.ref029","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1093\/annonc\/mdr011","article-title":"Pilot trial of sunitinib therapy in patients with von Hippel-Lindau disease","volume":"22","author":"E Jonasch","year":"2011","journal-title":"Ann Oncol"},{"issue":"34","key":"pone.0323979.ref030","doi-asserted-by":"crossref","first-page":"23390","DOI":"10.18632\/oncotarget.25171","article-title":"Pilot study of dovitinib in patients with von Hippel-Lindau disease","volume":"9","author":"P Pili\u00e9","year":"2018","journal-title":"Oncotarget"},{"issue":"10","key":"pone.0323979.ref031","article-title":"Infigratinib for the treatment of metastatic or locally advanced Cholangiocarcinoma with known FGFR2 gene fusions or rearrangements","volume":"15","author":"K White","year":"2023","journal-title":"Cureus"},{"key":"pone.0323979.ref032","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/B978-0-444-62702-5.00010-X","article-title":"Von Hippel-Lindau disease","volume":"132","author":"P Chittiboina","year":"2015","journal-title":"Handb Clin Neurol"},{"issue":"8","key":"pone.0323979.ref033","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1093\/bioinformatics\/bts091","article-title":"Unipro UGENE: a unified bioinformatics toolkit","volume":"28","author":"UGENE team.","year":"2012","journal-title":"Bioinformatics"},{"issue":"2","key":"pone.0323979.ref034","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0264011","article-title":"FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort","volume":"17","author":"T Schrumpf","year":"2022","journal-title":"PLoS One"},{"key":"pone.0323979.ref035","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/1756-0500-4-72","article-title":"FGFR2 protein expression in breast cancer: nuclear localisation and correlation with patient genotype","volume":"4","author":"AJ Martin","year":"2011","journal-title":"BMC Res Notes"},{"issue":"7","key":"pone.0323979.ref036","doi-asserted-by":"crossref","first-page":"490","DOI":"10.20892\/j.issn.2095-3941.2023.0137","article-title":"Current progress in cancer treatment by targeting FGFR signaling","volume":"20","author":"S Du","year":"2023","journal-title":"Cancer Biol Med"},{"issue":"1","key":"pone.0323979.ref037","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13045-022-01347-8","article-title":"The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis","volume":"15","author":"Y Huang","year":"2022","journal-title":"J Hematol Oncol"},{"issue":"9","key":"pone.0323979.ref038","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41419-020-02998-6","article-title":"PI3K\/AKT pathway as a key link modulates the multidrug resistance of cancers","volume":"11","author":"R Liu","year":"2020","journal-title":"Cell Death Dis"},{"issue":"9","key":"pone.0323979.ref039","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.4161\/cc.9.9.11483","article-title":"The Raf\/MEK\/ERK pathway can govern drug resistance, apoptosis and sensitivity to targeted therapy","volume":"9","author":"SL Abrams","year":"2010","journal-title":"Cell Cycle"},{"issue":"3","key":"pone.0323979.ref040","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.3892\/or.2014.3283","article-title":"Downregulation of fibroblast growth factor receptor 2 and its isoforms correlates with a high proliferation rate and poor prognosis in high-grade glioma","volume":"32","author":"R Ohashi","year":"2014","journal-title":"Oncol Rep"},{"issue":"1","key":"pone.0323979.ref041","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s40478-022-01363-2","article-title":"Fibroblast growth factor receptor 4 promotes glioblastoma progression: a central role of integrin-mediated cell invasiveness","volume":"10","author":"L Gabler","year":"2022","journal-title":"Acta Neuropathol Commun"},{"issue":"5","key":"pone.0323979.ref042","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1091\/mbc.e05-10-0987","article-title":"Neural cell adhesion molecule induces intracellular signaling via multiple mechanisms of Ca2+ homeostasis","volume":"17","author":"D Kiryushko","year":"2006","journal-title":"Mol Biol Cell"},{"issue":"2","key":"pone.0323979.ref043","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1152\/physrev.00031.2020","article-title":"Fluid transport in the brain","volume":"102","author":"MK Rasmussen","year":"2022","journal-title":"Physiol 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Genomics"},{"issue":"2","key":"pone.0323979.ref050","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1159\/000334707","article-title":"Submicroscopic deletion of FGFR1 gene is recurrently detected in myeloid and lymphoid neoplasms associated with ZMYM2-FGFR1 rearrangements: a case study","volume":"127","author":"JJ Yang","year":"2012","journal-title":"Acta Haematol"},{"issue":"10","key":"pone.0323979.ref051","first-page":"2794","article-title":"Fibroblast growth factor receptor gene expression and immunoreactivity are elevated in human glioblastoma multiforme","volume":"54","author":"RS Morrison","year":"1994","journal-title":"Cancer Res"},{"issue":"2","key":"pone.0323979.ref052","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1073\/pnas.91.2.484","article-title":"Differential expression of two fibroblast growth factor-receptor genes is associated with malignant progression in human astrocytomas","volume":"91","author":"F Yamaguchi","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pone.0323979.ref053","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00401-021-02327-x","article-title":"Targeting fibroblast growth factor receptors to combat aggressive ependymoma","volume":"142","author":"D L\u00f6tsch","year":"2021","journal-title":"Acta Neuropathol"},{"issue":"3","key":"pone.0323979.ref054","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1056\/NEJMoa2206834","article-title":"Futibatinib for FGFR2-rearranged intrahepatic Cholangiocarcinoma","volume":"388","author":"L Goyal","year":"2023","journal-title":"N Engl J Med"},{"issue":"10","key":"pone.0323979.ref055","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S2468-1253(21)00196-5","article-title":"Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study","volume":"6","author":"M Javle","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"3","key":"pone.0323979.ref056","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1177\/1078155220983425","article-title":"Fibroblast growth factor receptor (FGFR) inhibitors: a review of a novel therapeutic class","volume":"27","author":"A Weaver","year":"2021","journal-title":"J Oncol Pharm Pract"},{"issue":"5","key":"pone.0323979.ref057","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1093\/ajhp\/zxz329","article-title":"Erdafitinib: A novel therapy for FGFR-mutated urothelial cancer","volume":"77","author":"K Roubal","year":"2020","journal-title":"Am J Health Syst Pharm"},{"issue":"12","key":"pone.0323979.ref058","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1158\/2159-8290.CD-19-0555","article-title":"First-in-Human Phase I Study of Fisogatinib (BLU-554) validates Aberrant FGF19 signaling as a driver event in 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and neurosurgical treatment","volume":"36","author":"J-H Klingler","year":"2020","journal-title":"Childs Nerv Syst"},{"issue":"3","key":"pone.0323979.ref073","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1227\/01.NEU.0000153909.70381.C8","article-title":"Characterization of hemangioblastomas of spinal nerves","volume":"56","author":"S Gl\u00e4sker","year":"2005","journal-title":"Neurosurgery"},{"issue":"1","key":"pone.0323979.ref074","doi-asserted-by":"crossref","first-page":"11144","DOI":"10.1038\/s41598-018-29047-9","article-title":"Assessment of care pattern and outcome in hemangioblastoma","volume":"8","author":"Y Huang","year":"2018","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0323979.ref075","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.wneu.2014.06.018","article-title":"Clinical factors predicting outcomes after surgical resection for sporadic cerebellar hemangioblastomas","volume":"82","author":"M Fukuda","year":"2014","journal-title":"World Neurosurg"},{"issue":"6","key":"pone.0323979.ref076","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1055\/s-0043-1776707","article-title":"En Bloc resection for spinal cord hemangioblastomas: surgical technique and clinical outcomes","volume":"85","author":"X Chen","year":"2024","journal-title":"J Neurol Surg A Cent Eur Neurosurg"},{"issue":"2","key":"pone.0323979.ref077","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11060-022-04021-8","article-title":"Presentation, imaging, patterns of care, growth, and outcome in sporadic and von Hippel-Lindau-associated central nervous system hemangioblastomas","volume":"159","author":"H Takami","year":"2022","journal-title":"J Neurooncol"},{"issue":"9","key":"pone.0323979.ref078","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1093\/neuonc\/nox034","article-title":"Differences in genetic and epigenetic alterations between von Hippel-Lindau disease-related and 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