TY - JOUR
T1 - Expression of SSTR2a, FAP, HER2 and HER3 as potential radionuclide therapy targets in higher-grade meningioma
AU - Mair, Maximilian J.
AU - Hartenbach, Sabrina
AU - Tomasich, Erwin
AU - Maas, Sybren L.N.
AU - Bosch, Sarah A.
AU - Widhalm, Georg
AU - Eckert, Franziska
AU - Sahm, Felix
AU - Hainfellner, Johannes A.
AU - Hartenbach, Markus
AU - Berghoff, Anna S.
AU - Preusser, Matthias
AU - Albert, Nathalie L.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/1/16
Y1 - 2025/1/16
N2 - Purpose: High-grade meningiomas have high recurrence rates and limited prognosis. Radioligand therapies are approved in extracranial malignancies, but their value in brain tumours including meningiomas is unclear, as data on target expression is scarce. Methods: CNS WHO grade 2 and 3 meningioma samples were immunohistochemically stained for somatostatin receptor 2a (SSTR2a), fibroblast activation protein (FAP), and human epidermal growth factor receptors 2/3 (HER2/HER3). Target expression was correlated with (epi-)genetic tumour subtyping by DNA methylation analysis, genetic alterations, and survival. Results: Meningioma samples of 58 patients were included. SSTR2a expression (membranous/cytoplasmic) was observed in 43/55 (78.2%), and FAP expression in 15/58 (25.9%) evaluable samples, with HER2 and HER3 expression in one specimen each (1.7%). Membranous SSTR2a expression was strong in 18 (32.7%), intermediate in 12 (21.8%), and weak in 11 (20.0%) samples. While SSTR2a expression was more homogenous and mainly seen in regions with higher cellularity, FAP immunoreactivity was predominantly seen in tumour stroma and regions of lower cellularity. SSTR2a immunoreactivity was associated with TRAF7 wildtype status (p = 0.034). FAP expression was more frequent in meningiomas of CNS WHO grade 3 (vs. CNS WHO 2; p < 0.001), and samples with NF2 mutations (p = 0.032) or CDKN2A/B deletions (p = 0.013) compared to wildtype. FAP and SSTR2a expression (present vs. absent) were not associated with overall survival (p > 0.05). Conclusion: SSTR2a and FAP are expressed in high-grade meningioma samples to a variable extent, and differences across meningioma subtypes underscore the need for biomarkers to improve patient selection. Spatial heterogeneity of target expression should be considered in radioligand therapy design.
AB - Purpose: High-grade meningiomas have high recurrence rates and limited prognosis. Radioligand therapies are approved in extracranial malignancies, but their value in brain tumours including meningiomas is unclear, as data on target expression is scarce. Methods: CNS WHO grade 2 and 3 meningioma samples were immunohistochemically stained for somatostatin receptor 2a (SSTR2a), fibroblast activation protein (FAP), and human epidermal growth factor receptors 2/3 (HER2/HER3). Target expression was correlated with (epi-)genetic tumour subtyping by DNA methylation analysis, genetic alterations, and survival. Results: Meningioma samples of 58 patients were included. SSTR2a expression (membranous/cytoplasmic) was observed in 43/55 (78.2%), and FAP expression in 15/58 (25.9%) evaluable samples, with HER2 and HER3 expression in one specimen each (1.7%). Membranous SSTR2a expression was strong in 18 (32.7%), intermediate in 12 (21.8%), and weak in 11 (20.0%) samples. While SSTR2a expression was more homogenous and mainly seen in regions with higher cellularity, FAP immunoreactivity was predominantly seen in tumour stroma and regions of lower cellularity. SSTR2a immunoreactivity was associated with TRAF7 wildtype status (p = 0.034). FAP expression was more frequent in meningiomas of CNS WHO grade 3 (vs. CNS WHO 2; p < 0.001), and samples with NF2 mutations (p = 0.032) or CDKN2A/B deletions (p = 0.013) compared to wildtype. FAP and SSTR2a expression (present vs. absent) were not associated with overall survival (p > 0.05). Conclusion: SSTR2a and FAP are expressed in high-grade meningioma samples to a variable extent, and differences across meningioma subtypes underscore the need for biomarkers to improve patient selection. Spatial heterogeneity of target expression should be considered in radioligand therapy design.
UR - http://www.scopus.com/inward/record.url?scp=85218131877&partnerID=8YFLogxK
U2 - 10.1007/s00259-025-07075-8
DO - 10.1007/s00259-025-07075-8
M3 - Article
C2 - 39969538
AN - SCOPUS:85218131877
SN - 1619-7070
VL - 52
SP - 2771
EP - 2781
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
IS - 8
ER -