{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:22:52Z","timestamp":1791645772041,"version":"4.3.4"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4t Augsburg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and a major cause of mortality in neurofibromatosis type 1 (NF-1). Distinguishing MPNSTs from benign neurofibromas remains challenging. We investigated fibroblast activation protein alpha (FAP) as a malignancy biomarker and theranostic target in peripheral nerve sheath tumors.\u00a0Therefore, we integrated publicly available bulk transcriptomics, spatial transcriptomics, and single-cell RNA sequencing with immunohistochemistry (IHC) on independent archival samples. We further directly assessed clinical translatability using FAP-targeted PET\/CT in an NF-1 patient undergoing work-up for suspected malignant transformation. Across independent bulk datasets,\n                    <jats:italic>FAP<\/jats:italic>\n                    was consistently up-regulated in MPNSTs compared with neurofibromas. In the TCGA sarcoma dataset,\n                    <jats:italic>FAP<\/jats:italic>\n                    varied by histotype but was clearly expressed in MPNSTs. Spatial transcriptomics revealed enrichment of\n                    <jats:italic>FAP<\/jats:italic>\n                    -high regions in MPNSTs and co-localization with tumor cell markers. Single-cell analysis showed\n                    <jats:italic>FAP<\/jats:italic>\n                    expression in MPNST tumor cells and cancer-associated fibroblasts, with the highest levels in neural crest-like tumor subpopulations previously linked to adverse prognosis; pseudotime analysis indicated decreasing\n                    <jats:italic>FAP<\/jats:italic>\n                    expression along trajectories toward Schwann cell precursor-like states linking\n                    <jats:italic>FAP<\/jats:italic>\n                    expression to a more primitive, dedifferentiated tumor cell state. IHC confirmed strong, predominantly tumor cell-intrinsic FAP expression in MPNSTs, with minimal staining in neurofibromas and normal tissues. Plexiform neurofibromas exhibited intermediate FAP expression. In clinical imaging, FAP-PET demonstrated higher tracer uptake in histologically proven MPNSTs than in benign lesions within the same patient, including a neurofibroma that was FDG-avid but FAP-negative, supporting added diagnostic specificity over FDG-PET\/CT. In summary,\u00a0FAP is robustly overexpressed in MPNSTs at transcript and protein levels, potentially concentrates in high-risk tumor cell states, and is detectable by targeted PET imaging. These findings identify FAP as a clinically relevant biomarker for malignancy in NF-1-associated tumors and support implementation of FAP-directed diagnostics and therapeutics in peripheral nerve sheath tumor work-up.\n                  <\/jats:p>","DOI":"10.1007\/s00401-026-02979-7","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T10:49:29Z","timestamp":1769510969000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["FAP expression as a marker of malignant transformation enabling in vivo characterization in peripheral nerve sheath tumors: a multimodal and translational study"],"prefix":"10.1007","volume":"151","author":[{"given":"Nic G.","family":"Reitsam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"G\u00e4ble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Siebenh\u00fcter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Schaller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Liesche-Starnecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Sipos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Dintner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Walz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Babic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Trepel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Kircher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria E.","family":"Fincke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal D.","family":"Johann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"M\u00e4rkl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Lapa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna S.","family":"Enke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"2979_CR1","doi-asserted-by":"crossref","unstructured":"Ferner RE (2007) Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. Lancet Neurology 6","DOI":"10.1016\/S1474-4422(07)70075-3"},{"key":"2979_CR2","doi-asserted-by":"publisher","DOI":"10.47391\/JPMA.4612","author":"F Iqbal","year":"2023","unstructured":"Iqbal F, Jamaluddin M, Bukhari F, Islam OS (2023) Malignant peripheral nerve sheath tumours in a patient with Neurofibromatosis-1. J Pak Med Assoc. https:\/\/doi.org\/10.47391\/JPMA.4612","journal-title":"J Pak Med Assoc"},{"key":"2979_CR3","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/756395","author":"DE Porter","year":"2009","unstructured":"Porter DE, Prasad V, Foster L, Dall GF, Birch R, Grimer RJ (2009) Survival in malignant peripheral nerve sheath tumours: a comparison between sporadic and neurofibromatosis type 1-associated tumours. Sarcoma. https:\/\/doi.org\/10.1155\/2009\/756395","journal-title":"Sarcoma"},{"key":"2979_CR4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.65.3576","author":"E Uusitalo","year":"2016","unstructured":"Uusitalo E, Rantanen M, Kallionp\u00e4\u00e4 RA, P\u00f6yh\u00f6nen M, Lepp\u00e4virta J, Yl\u00e4-Outinen H et al (2016) Distinctive cancer associations in patients with neurofibromatosis type 1. J Clin Oncol. https:\/\/doi.org\/10.1200\/JCO.2015.65.3576","journal-title":"J Clin Oncol"},{"key":"2979_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/S0748-7983(03)00055-6","author":"S Cardona","year":"2003","unstructured":"Cardona S, Schwarzbach M, Hinz U, Dimitrakopoulou-Strauss A, Attigah A, Mechtersheimer G et al (2003) Evaluation of F18-deoxyglucose positron emission tomography (FDG-PET) to assess the nature of neurogenic tumours. Eur J Surg Oncol. https:\/\/doi.org\/10.1016\/S0748-7983(03)00055-6","journal-title":"Eur J Surg Oncol"},{"key":"2979_CR6","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.114.142372","author":"A Chirindel","year":"2015","unstructured":"Chirindel A, Chaudhry M, Blakeley JO, Wahl R (2015) 18F-FDG PET\/CT qualitative and quantitative evaluation in neurofibromatosis type 1 patients for detection of malignant transformation: Comparison of early to delayed imaging with and without liver activity normalization. J Nucl Med. https:\/\/doi.org\/10.2967\/jnumed.114.142372","journal-title":"J Nucl Med"},{"key":"2979_CR7","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-021-03936-y","author":"RTJ Geitenbeek","year":"2022","unstructured":"Geitenbeek RTJ, Martin E, Graven LH, Broen MPG, Anten MHME, van der Pol JAJ et al (2022) Diagnostic value of 18F-FDG PET-CT in detecting malignant peripheral nerve sheath tumors among adult and pediatric neurofibromatosis type 1 patients. J Neurooncol. https:\/\/doi.org\/10.1007\/s11060-021-03936-y","journal-title":"J Neurooncol"},{"key":"2979_CR8","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noy013","author":"CS Higham","year":"2018","unstructured":"Higham CS, Dombi E, Rogiers A, Bhaumik S, Pans S, Connor SEJ et al (2018) The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheath tumors. Neuro Oncol. https:\/\/doi.org\/10.1093\/neuonc\/noy013","journal-title":"Neuro Oncol"},{"key":"2979_CR9","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djx124","author":"KM Reilly","year":"2017","unstructured":"Reilly KM, Kim AR, Blakely J, Ferner RE, Gutmann DH, Legius E et al (2017) Neurofibromatosis type 1\u2013associated MPNST state of the science: outlining a research agenda for the future. J Natl Cancer Inst. https:\/\/doi.org\/10.1093\/jnci\/djx124","journal-title":"J Natl Cancer Inst"},{"key":"2979_CR10","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6162182","author":"D Tovmassian","year":"2016","unstructured":"Tovmassian D, Abdul Razak M, London K (2016) The role of [18F]FDG-PET\/CT in predicting malignant transformation of plexiform neurofibromas in neurofibromatosis-1. Int J Surg Oncol. https:\/\/doi.org\/10.1155\/2016\/6162182","journal-title":"Int J Surg Oncol"},{"key":"2979_CR11","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/2480493","author":"JN Crane","year":"2023","unstructured":"Crane JN, Graham DS, Mona CE, Nelson SD, Samiei A, Dawson DW et al (2023) Fibroblast activation protein expression in sarcomas. Sarcoma. https:\/\/doi.org\/10.1155\/2023\/2480493","journal-title":"Sarcoma"},{"key":"2979_CR12","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.92232","author":"A Lo","year":"2017","unstructured":"Lo A, Li CP, Buza EL, Blomberg R, Govindaraju P, Avery D et al (2017) Fibroblast activation protein augments progression and metastasis of pancreatic ductal adenocarcinoma. JCI Insight. https:\/\/doi.org\/10.1172\/jci.insight.92232","journal-title":"JCI Insight"},{"key":"2979_CR13","doi-asserted-by":"crossref","unstructured":"Glantschnig L, Reitsam NG, Kircher Malte MD, Segmiller D, Lapa C, Dierks A (2025) Intense FAP expression of ovarian metastatic breast cancer detected by [68Ga]RTX-1363 PET\/CT. Clin Nucl Med 50","DOI":"10.1097\/RLU.0000000000005689"},{"key":"2979_CR14","doi-asserted-by":"publisher","DOI":"10.3389\/pore.2023.1611163","author":"K Greimelmaier","year":"2023","unstructured":"Greimelmaier K, Klopp N, Mairinger E, Wessolly M, Borchert S, Steinborn J et al (2023) Fibroblast activation protein-\u03b1 expression in fibroblasts is common in the tumor microenvironment of colorectal cancer and may serve as a therapeutic target. Pathol Oncol Res. https:\/\/doi.org\/10.3389\/pore.2023.1611163","journal-title":"Pathol Oncol Res"},{"key":"2979_CR15","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i8.840","author":"M Shi","year":"2012","unstructured":"Shi M, Yu DH, Chen Y, Zhao CY, Zhang J, Liu QH et al (2012) Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance. World J Gastroenterol. https:\/\/doi.org\/10.3748\/wjg.v18.i8.840","journal-title":"World J Gastroenterol"},{"key":"2979_CR16","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.648187","author":"L Xin","year":"2021","unstructured":"Xin L, Gao J, Zheng Z, Chen Y, Lv S, Zhao Z et al (2021) Fibroblast activation protein-\u03b1 as a target in the bench-to-bedside diagnosis and treatment of tumors: a narrative review. Front Oncol. https:\/\/doi.org\/10.3389\/fonc.2021.648187","journal-title":"Front Oncol"},{"key":"2979_CR17","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.120.259192","author":"RP Baum","year":"2022","unstructured":"Baum RP, Schuchardt C, Singh A, Chantadisai M, Robiller FC, Zhang J et al (2022) Feasibility, biodistribution, and preliminary dosimetry in peptide-targeted radionuclide therapy of diverse adenocarcinomas using 177Lu-FAP-2286: first-in-humans results. J Nucl Med. https:\/\/doi.org\/10.2967\/jnumed.120.259192","journal-title":"J Nucl Med"},{"key":"2979_CR18","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1007\/s00259-024-06914-4","volume":"52","author":"H Ceuppens","year":"2025","unstructured":"Ceuppens H, Pombo Antunes AR, Navarro L, Ertveldt T, Berdal M, Nagachinta S et al (2025) Efficient \u03b1 and \u03b2\u2212 radionuclide therapy targeting fibroblast activation protein-\u03b1 in an aggressive preclinical mouse tumour model. Eur J Nucl Med Mol Imaging 52:444\u2013457. https:\/\/doi.org\/10.1007\/s00259-024-06914-4","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2979_CR19","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2238","author":"M Fabre","year":"2020","unstructured":"Fabre M, Ferrer C, Dom\u00ednguez-Hormaetxe S, Bockorny B, Murias L, Seifert O et al (2020) OMTX705, a novel FAP-targeting ADC demonstrates activity in chemotherapy and pembrolizumab-resistant solid tumor models. Clin Cancer Res. https:\/\/doi.org\/10.1158\/1078-0432.CCR-19-2238","journal-title":"Clin Cancer Res"},{"key":"2979_CR20","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-1432","author":"WP Fendler","year":"2022","unstructured":"Fendler WP, Pabst KM, Kessler L, Costa PF, Ferdinandus J, Weber M et al (2022) Safety and efficacy of 90Y-FAPI-46 radioligand therapy in patients with advanced sarcoma and other cancer entities. Clin Cancer Res. https:\/\/doi.org\/10.1158\/1078-0432.CCR-22-1432","journal-title":"Clin Cancer Res"},{"key":"2979_CR21","doi-asserted-by":"crossref","unstructured":"Hirmas N, Hamacher R, Sraieb M, Ingenwerth M, Kessler L, Pabst KM, Barbato F, Lueckerath K, Kasper S, Nader M, Schildhaus HU, Kesch C, von Tresckow B, Hanoun C, Hautzel H, Aigner C, Glas M, Stuschke M, K\u00fcmmel S, Harter P, Lugnier C, Uhl W, Niedergethmann M, Hadaschik B, Gr\u00fcnwald V, Siveke JT, Herrmann K, Fendler WP (2023) Fibroblast-activation protein PET and histopathology in a single-center database of 324 patients and 21 tumor entities. J Nucl Med 64","DOI":"10.2967\/jnumed.122.264689"},{"key":"2979_CR22","doi-asserted-by":"publisher","first-page":"880","DOI":"10.2967\/jnumed.123.267248","volume":"65","author":"H Lanzafame","year":"2024","unstructured":"Lanzafame H, Mavroeidi IA, Pabst KM, Desaulniers M, Ingenwerth M, Hirmas N et al (2024) 68 Ga-fibroblast activation protein inhibitor PET\/CT improves detection of intermediate and low-grade sarcomas and identifies candidates for radiopharmaceutical therapy. J Nucl Med 65:880. https:\/\/doi.org\/10.2967\/jnumed.123.267248","journal-title":"J Nucl Med"},{"key":"2979_CR23","doi-asserted-by":"publisher","unstructured":"Pang Y, Zhao L, Meng T, Xu W, Lin Q, Wu H, Zhang J, Chen X, Sun L, Chen H (2023) PET imaging of fibroblast activation protein in various types of cancer using 68Ga-FAP-2286: comparison with 18F-FDG and 68Ga-FAPI-46 in a single-center, prospective study. J Nucl Med. https:\/\/doi.org\/10.2967\/jnumed.122.264544","DOI":"10.2967\/jnumed.122.264544"},{"key":"2979_CR24","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.123.266393","author":"AM Spektor","year":"2024","unstructured":"Spektor AM, Gutjahr E, Lang M, Glatting FM, Hackert T, Pausch T et al (2024) Immunohistochemical FAP expression reflects 68Ga-FAPI PET imaging properties of low- and high-grade intraductal papillary mucinous neoplasms and pancreatic ductal adenocarcinoma. J Nucl Med. https:\/\/doi.org\/10.2967\/jnumed.123.266393","journal-title":"J Nucl Med"},{"key":"2979_CR25","doi-asserted-by":"publisher","first-page":"4026","DOI":"10.1007\/s00259-024-06809-4","volume":"51","author":"MF Taddio","year":"2024","unstructured":"Taddio MF, Doshi S, Masri M, Jeanjean P, Hikmat F, Gerlach A et al (2024) Evaluating [225Ac]Ac-FAPI-46 for the treatment of soft-tissue sarcoma in mice. Eur J Nucl Med Mol Imaging 51:4026\u20134037. https:\/\/doi.org\/10.1007\/s00259-024-06809-4","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2979_CR26","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.3c00244","author":"A Zana","year":"2023","unstructured":"Zana A, Puig-Moreno C, Bocci M, Gilardoni E, Di Nitto C, Principi L et al (2023) A comparative analysis of fibroblast activation protein-targeted small molecule-drug, antibody-drug, and peptide-drug conjugates. Bioconjug Chem. https:\/\/doi.org\/10.1021\/acs.bioconjchem.3c00244","journal-title":"Bioconjug Chem"},{"key":"2979_CR27","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-0954-z","author":"FJ Rodriguez","year":"2012","unstructured":"Rodriguez FJ, Folpe AL, Giannini C, Perry A (2012) Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. Acta Neuropathol. https:\/\/doi.org\/10.1007\/s00401-012-0954-z","journal-title":"Acta Neuropathol"},{"key":"2979_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20603-4","author":"C Koelsche","year":"2021","unstructured":"Koelsche C, Schrimpf D, Stichel D, Sill M, Sahm F, Reuss DE et al (2021) Sarcoma classification by DNA methylation profiling. Nat Commun. https:\/\/doi.org\/10.1038\/s41467-020-20603-4","journal-title":"Nat Commun"},{"issue":"8","key":"2979_CR29","first-page":"716","volume":"109","author":"KS Mccarty","year":"1985","unstructured":"Mccarty KS, Miller LS, Cox EB, Konrath JG, Mccarty KS (1985) Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med 109(8):716\u2013721","journal-title":"Arch Pathol Lab Med"},{"key":"2979_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104829","author":"M H\u00f8land","year":"2023","unstructured":"H\u00f8land M, Berg KCG, Eilertsen IA, Bjerkehagen B, Kolberg M, Boye K et al (2023) Transcriptomic subtyping of malignant peripheral nerve sheath tumours highlights immune signatures, genomic profiles, patient survival and therapeutic targets. EBioMedicine. https:\/\/doi.org\/10.1016\/j.ebiom.2023.104829","journal-title":"EBioMedicine"},{"key":"2979_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2015.02.005","author":"M Kolberg","year":"2015","unstructured":"Kolberg M, H\u00f8land M, Lind GE, \u00c5gesen TH, Skotheim RI, Sundby Hall K et al (2015) Protein expression of BIRC5, TK1, and TOP2A in malignant peripheral nerve sheath tumours - A prognostic test after surgical resection. Mol Oncol. https:\/\/doi.org\/10.1016\/j.molonc.2015.02.005","journal-title":"Mol Oncol"},{"key":"2979_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.014","author":"A Abeshouse","year":"2017","unstructured":"Abeshouse A, Adebamowo C, Adebamowo SN, Akbani R, Akeredolu T, Ally A et al (2017) Comprehensive and integrated genomic characterization of adult soft tissue sarcomas. Cell. https:\/\/doi.org\/10.1016\/j.cell.2017.10.014","journal-title":"Cell"},{"key":"2979_CR33","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095","author":"E Cerami","year":"2012","unstructured":"Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA et al (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. https:\/\/doi.org\/10.1158\/2159-8290.CD-12-0095","journal-title":"Cancer Discov"},{"key":"2979_CR34","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088","author":"J Gao","year":"2013","unstructured":"Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. https:\/\/doi.org\/10.1126\/scisignal.2004088","journal-title":"Sci Signal"},{"key":"2979_CR35","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaf016","author":"J Bremer","year":"2025","unstructured":"Bremer J, Franco P, Menstell JA, Tey S, Zajt KK, Popzhelyazkova K et al (2025) Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors. Neuro Oncol. https:\/\/doi.org\/10.1093\/neuonc\/noaf016","journal-title":"Neuro Oncol"},{"key":"2979_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048","author":"Y Hao","year":"2021","unstructured":"Hao Y, Hao S, Andersen-Nissen E, Mauck WM, Zheng S, Butler A et al (2021) Integrated analysis of multimodal single-cell data. Cell. https:\/\/doi.org\/10.1016\/j.cell.2021.04.048","journal-title":"Cell"},{"key":"2979_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y","author":"Y Hao","year":"2024","unstructured":"Hao Y, Stuart T, Kowalski MH, Choudhary S, Hoffman P, Hartman A et al (2024) Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat Biotechnol. https:\/\/doi.org\/10.1038\/s41587-023-01767-y","journal-title":"Nat Biotechnol"},{"key":"2979_CR38","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo5442","author":"LMN Wu","year":"2022","unstructured":"Wu LMN, Zhang F, Rao R, Adam M, Pollard K, Szabo S et al (2022) Single-cell multiomics identifies clinically relevant mesenchymal stem-like cells and key regulators for MPNST malignancy. Sci Adv. https:\/\/doi.org\/10.1126\/sciadv.abo5442","journal-title":"Sci Adv"},{"key":"2979_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4772-0","author":"K Street","year":"2018","unstructured":"Street K, Risso D, Fletcher RB, Das D, Ngai J, Yosef N et al (2018) Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genom. https:\/\/doi.org\/10.1186\/s12864-018-4772-0","journal-title":"BMC Genom"},{"key":"2979_CR40","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323","author":"B Li","year":"2011","unstructured":"Li B, Dewey CN (2011) RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics. https:\/\/doi.org\/10.1186\/1471-2105-12-323","journal-title":"BMC Bioinformatics"},{"key":"2979_CR41","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.160","author":"BS Misemer","year":"2014","unstructured":"Misemer BS, Skubitz APN, Carlos Manivel J, Schmechel SC, Cheng EY, Henriksen JC et al (2014) Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity. Cancer Med. https:\/\/doi.org\/10.1002\/cam4.160","journal-title":"Cancer Med"},{"key":"2979_CR42","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-2548","author":"DK Mitchell","year":"2024","unstructured":"Mitchell DK, Burgess B, White EE, Smith AE, Sierra Potchanant EA, Mang H et al (2024) Spatial gene-expression profiling unveils immuno-oncogenic programs of NF1-associated peripheral nerve sheath tumor progression. Clin Cancer Res. https:\/\/doi.org\/10.1158\/1078-0432.CCR-23-2548","journal-title":"Clin Cancer Res"},{"key":"2979_CR43","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.200900027","author":"SJ Miller","year":"2009","unstructured":"Miller SJ, Jessen WJ, Mehta J, Hardiman A, Sites E, Kaiser S et al (2009) Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene. EMBO Mol Med. https:\/\/doi.org\/10.1002\/emmm.200900027","journal-title":"EMBO Mol Med"},{"key":"2979_CR44","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000168830.79997.13","author":"T Tucker","year":"2005","unstructured":"Tucker T, Wolkenstein P, Revuz J, Zeller J, Friedman JM (2005) Association between benign and malignant peripheral nerve sheath tumors in NF1. Neurology. https:\/\/doi.org\/10.1212\/01.wnl.0000168830.79997.13","journal-title":"Neurology"},{"key":"2979_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38432-6","author":"S Suppiah","year":"2023","unstructured":"Suppiah S, Mansouri S, Mamatjan Y, Liu JC, Bhunia MM, Patil V et al (2023) Multiplatform molecular profiling uncovers two subgroups of malignant peripheral nerve sheath tumors with distinct therapeutic vulnerabilities. Nat Commun. https:\/\/doi.org\/10.1038\/s41467-023-38432-6","journal-title":"Nat Commun"},{"key":"2979_CR46","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.27.620479","author":"T Pellinen","year":"2024","unstructured":"Pellinen T, Luomala L, Mattila KE, Hemmes A, V\u00e4lim\u00e4ki K, Br\u00fcck O et al (2024) Fibroblast activation protein defines aggressive EMT-associated cancer cell state and prognosis in localized ccRCC. bioRxiv. https:\/\/doi.org\/10.1101\/2024.10.27.620479","journal-title":"bioRxiv"},{"key":"2979_CR47","doi-asserted-by":"publisher","DOI":"10.1101\/765743","author":"Q Wu","year":"2019","unstructured":"Wu Q, Zhao M, Huang G, Zheng Z, Zeng W, Lv X (2019) FAP overexpression induce epithelial-mesenchymal transition (EMT) in oral squamous cell carcinoma by down-regulating DPP9 gene. bioRxiv. https:\/\/doi.org\/10.1101\/765743","journal-title":"bioRxiv"},{"key":"2979_CR48","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1210004","author":"P Beer","year":"2023","unstructured":"Beer P, Pauli C, Haberecker M, Grest P, Beebe E, Fuchs D et al (2023) Cross-species evaluation of fibroblast activation protein alpha as potential imaging target for soft tissue sarcoma: a comparative immunohistochemical study in humans, dogs, and cats. Front Oncol. https:\/\/doi.org\/10.3389\/fonc.2023.1210004","journal-title":"Front Oncol"},{"key":"2979_CR49","doi-asserted-by":"crossref","unstructured":"Gorrell MD, Gysbers V, McCaughan GW (2001) CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scand J Immunol 54","DOI":"10.1046\/j.1365-3083.2001.00984.x"},{"key":"2979_CR50","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-023-06211-6","author":"D Zboralski","year":"2023","unstructured":"Zboralski D, Osterkamp F, Christensen E, Bredenbeck A, Schumann A, Hoehne A et al (2023) Fibroblast activation protein targeted radiotherapy induces an immunogenic tumor microenvironment and enhances the efficacy of PD-1 immune checkpoint inhibition. Eur J Nucl Med Mol Imaging. https:\/\/doi.org\/10.1007\/s00259-023-06211-6","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2979_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-01103-4","author":"JP Brosseau","year":"2021","unstructured":"Brosseau JP, Sathe AA, Wang Y, Nguyen T, Glass DA, Xing C et al (2021) Human cutaneous neurofibroma matrisome revealed by single-cell RNA sequencing. Acta Neuropathol Commun. https:\/\/doi.org\/10.1186\/s40478-020-01103-4","journal-title":"Acta Neuropathol Commun"},{"key":"2979_CR52","doi-asserted-by":"crossref","unstructured":"Pi\u00f1a AR, Mart\u00ednez MM, de Almeida OP (2015) Glut-1, best immunohistochemical marker for perineurial cells. Head Neck Pathol 9","DOI":"10.1007\/s12105-014-0544-6"},{"key":"2979_CR53","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000003716","author":"J Wu","year":"2021","unstructured":"Wu J, Wang Y, Zhang C (2021) Increased 68Ga-FAPI uptake in neurofibromatosis in a patient with pleomorphic rhabdomyosarcoma. Clin Nucl Med. https:\/\/doi.org\/10.1097\/RLU.0000000000003716","journal-title":"Clin Nucl Med"},{"key":"2979_CR54","doi-asserted-by":"crossref","unstructured":"Zhu Y, Wu J, Wang Y, Geng J, Zhang C (2022) Presacral benign schwannoma mimics malignancy on 18F-FDG and 68Ga-FAPI PET\/CT. Clin Nucl Med 47","DOI":"10.1097\/RLU.0000000000003933"},{"key":"2979_CR55","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000564","author":"CN Prieto-Granada","year":"2016","unstructured":"Prieto-Granada CN, Wiesner T, Messina JL, Jungbluth AA, Chi P, Antonescu CR (2016) Loss of H3K27me3 expression is a highly sensitive marker for sporadic and radiation-induced MPNST. Am J Surg Pathol. https:\/\/doi.org\/10.1097\/PAS.0000000000000564","journal-title":"Am J Surg Pathol"},{"key":"2979_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2017.05.010","author":"MM Miettinen","year":"2017","unstructured":"Miettinen MM, Antonescu CR, Fletcher CDM, Kim A, Lazar AJ, Quezado MM et al (2017) Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1\u2014a consensus overview. Hum Pathol. https:\/\/doi.org\/10.1016\/j.humpath.2017.05.010","journal-title":"Hum Pathol"},{"key":"2979_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.11.002","author":"M Sill","year":"2025","unstructured":"Sill M, Schrimpf D, Patel A, Sturm D, J\u00e4ger N, Sievers P et al (2025) Advancing CNS tumor diagnostics with expanded DNA methylation-based classification. Cancer Cell. https:\/\/doi.org\/10.1016\/j.ccell.2025.11.002","journal-title":"Cancer Cell"},{"key":"2979_CR58","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.125.269572","author":"H Lanzafame","year":"2025","unstructured":"Lanzafame H, Heilig CE, Wardelmann E, Desaulniers M, Pabst KM, Mavroeidi IA et al (2025) 90Y-FAPI-46 theranostics leads to near-complete metabolic response in 3 patients with solitary fibrous tumors. J Nucl Med. https:\/\/doi.org\/10.2967\/jnumed.125.269572","journal-title":"J Nucl Med"},{"key":"2979_CR59","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010212","volume":"13","author":"J Chen","year":"2025","unstructured":"Chen J, Zhou Y, Pang Y, Fu K, Luo Q, Sun L et al (2025) FAP-targeted radioligand therapy with 68Ga 177Lu-DOTA-2P(FAPI) enhance immunogenicity and synergize with PD-L1 inhibitors for improved antitumor efficacy. J Immunother Cancer 13:e010212. https:\/\/doi.org\/10.1136\/jitc-2024-010212","journal-title":"J Immunother Cancer"},{"key":"2979_CR60","doi-asserted-by":"crossref","unstructured":"Paudel SN, Hutzen B, Cripe TP (2023) The quest for effective immunotherapies against malignant peripheral nerve sheath tumors: is there hope? Mol Ther Oncolytics 30","DOI":"10.1016\/j.omto.2023.07.008"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-02979-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-026-02979-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-02979-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T10:49:32Z","timestamp":1769510972000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-026-02979-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["2979"],"URL":"https:\/\/doi.org\/10.1007\/s00401-026-02979-7","relation":{},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]},"assertion":[{"value":"20 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"NGR received travel support from Bruker Spatial Biology, unrelated to this study. CL reports prior consulting activities for Blue Earth Diagnostics Ltd. and Novartis. JSE received travel support from Boston Scientific Medizintechnik GmbH, unrelated to this study.  JB is an employee and shareholder at Ratio Therapeutics.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Our study was approved by the responsible ethical committee of Ludwig-Maximilians-University of Munich (reference: project number 25-0654) and was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained by the involved patients. For analyses involving publicly available transcriptomic datasets, we refer to the original publications for details regarding ethical approval and patient consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}],"article-number":"11"}}