Puttonen Maya, Tynninen Olli, Salmikangas Sami, Vesterinen Tiina, Sihto Harri, Böhling Tom
Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Department of Pathology, HUSLAB, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
PLoS One. 2025 May 20;20(5):e0323979. doi: 10.1371/journal.pone.0323979. eCollection 2025.
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.
血管母细胞瘤是中枢神经系统中一种血管高度丰富的良性肿瘤，常与冯·希佩尔-林道（VHL）病相关。血管母细胞瘤可能导致肿瘤相关出血或对附近结构施加压力，从而引发危及生命的并发症。尽管手术切除是主要治疗方法，但完全切除并不总是可行的。因此，有必要探索靶向治疗或抗血管生成疗法。成纤维细胞生长因子受体（FGFR）家族在肿瘤发生和血管生成中起作用，使其成为个性化治疗的潜在靶点。FGFRs在血管母细胞瘤中的分布和意义尚未得到研究。我们检查了来自111例患者的139份福尔马林固定、石蜡包埋的血管母细胞瘤样本，包括散发性病例和与VHL病相关的病例。免疫组织化学显示FGFR2（95%）和FGFR4（61%）呈阳性染色，而FGFR1（0%）和FGFR3（12%）主要为阴性。FGFR2表达在VHL突变肿瘤（75%，p = 0.034）和男性患者（68%，p = 0.020）中显著增加。位于大脑的肿瘤（n = 6，5%）FGFR4染色阳性的可能性更高（100%，p = 0.009）。此外，肿瘤直径越大，FGFR4表达的可能性越高（中位数12.0毫米对17.5毫米，p = 0.018），表明其在肿瘤生长中的作用。我们的研究揭示了FGFR2和FGFR4在大量血管母细胞瘤中的表达。这一发现证明了FGFRs作为血管母细胞瘤患者有前景的治疗靶点的潜力。
