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@ARTICLE{Mair:298982,
author = {M. J. Mair and S. Hartenbach and E. Tomasich and S. L. N.
Maas and S. A. Bosch and G. Widhalm and F. Eckert and F.
Sahm$^*$ and J. A. Hainfellner and M. Hartenbach and A. S.
Berghoff and M. Preusser and N. L. Albert$^*$},
title = {{E}xpression of {SSTR}2a, {FAP}, {HER}2 and {HER}3 as
potential radionuclide therapy targets in higher-grade
meningioma.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {52},
number = {8},
issn = {1619-7070},
address = {Heidelberg [u.a.]},
publisher = {Springer-Verl.},
reportid = {DKFZ-2025-00402},
pages = {2771-2781},
year = {2025},
note = {2025 Jul;52(8):2771-2781},
abstract = {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.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.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).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.},
keywords = {Brain tumour (Other) / Fibroblast activating protein
(Other) / Meningioma (Other) / Somatostatin receptor (Other)
/ Theranostics (Other)},
cin = {B300 / HD01 / MU01},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)MU01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39969538},
doi = {10.1007/s00259-025-07075-8},
url = {https://inrepo02.dkfz.de/record/298982},
}