{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:06:48Z","timestamp":1788948408064,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"abstract":"Abstract<\/jats:title>\n \n Fibroblast growth factor receptor 1 (\n FGFR1<\/jats:italic>\n ) amplification, a significant cancer alteration with both prognostic and therapeutic relevance, lacks a standardized definition. The relationship between\n FGFR1<\/jats:italic>\n copy number (CN) variations and tumour microenvironment (TME) characteristics also remains poorly understood. This study defined\n FGFR1<\/jats:italic>\n amplification and investigated TME features across\n FGFR1<\/jats:italic>\n CN subtypes in triple\u2010negative breast cancer (TNBC) to guide precise treatment. We analysed 182 TNBC tumour specimens.\n FGFR1<\/jats:italic>\n CN status was assessed using fluorescence\n in situ<\/jats:italic>\n hybridization (FISH). Next\u2010generation sequencing (NGS) was performed on 88 samples to explore biological differences. Immunohistochemical (IHC) results for CD3, CD4, and CD8 along with clinical data were analysed. Samples were categorized into four groups based on the\n FGFR1\/<\/jats:italic>\n CEN8 ratio and the mean\n FGFR1<\/jats:italic>\n signals per cell. Groups 1 (ratio\u2009\u2265\u20092.0, signals\u2009\u2265\u20094.0) and 2 (ratio\u2009\u2265\u20092.0, signals\u2009<\u20094.0) exhibited robust tumour proliferation, increased\n FGFR<\/jats:italic>\n signalling, and an immunosuppressive TME. Conversely, group 4 (ratio\u2009<\u20092.0, signals\u2009<\u20094.0) showed significantly enhanced immune cell infiltration (e.g. CD8\n +<\/jats:sup>\n T cells, NK cells), supported by elevated CD3\n +<\/jats:sup>\n \/CD8\n +<\/jats:sup>\n T\u2010cell densities. Group 3 (ratio\u2009<\u20092.0, signals\u2009\u2265\u20094.0) was heterogeneous: tumours with\n FGFR1<\/jats:italic>\n CN\u2009\u2265\u20095 resembled groups 1\/2, while those with CN\u2009<\u20095 mirrored group 4. Thus,\n FGFR1<\/jats:italic>\n amplification (\n FGFR1<\/jats:italic>\n \u2010Amp) was defined as\n FGFR1\/<\/jats:italic>\n CEN8 ratio\u2009\u2265\u20092.0 or CN\u2009\u2265\u20095.0 (14.29% prevalence, 26\/182). Remaining cases were\n FGFR1<\/jats:italic>\n \u2010neutral (\n FGFR1<\/jats:italic>\n \u2010Neu). Immune profiling revealed that\n FGFR1<\/jats:italic>\n \u2010Amp\u2009&\u2009HER2\u2010low TNBC had reduced immune cell infiltration but heightened oncogenic signalling (including epithelial\u2013mesenchymal transition, angiogenesis) compared with other subgroups. In contrast,\n FGFR1<\/jats:italic>\n \u2010Neu tumours, especially HER2\u2010zero, displayed increased immune cell infiltration (NK cells, effector cells), MHC I\/II molecules, activation markers, and elevated immune checkpoint expression (e.g.\n PD\u2010L1<\/jats:italic>\n ,\n CTLA4<\/jats:italic>\n ,\n LAG3<\/jats:italic>\n ). This study defines\n FGFR1<\/jats:italic>\n amplification in TNBC and characterizes its TME.\n FGFR1<\/jats:italic>\n \u2010Amp in HER2\u2010low TNBC correlates with an immunosuppressive environment, potentially hindering HER2\u2010ADC efficacy and suggesting combined\n FGFR<\/jats:italic>\n inhibition. Conversely,\n FGFR1<\/jats:italic>\n \u2010Neu\u2009&\u2009HER2\u2010zero tumours with immune activation may respond better to immunotherapy. \u00a9 2026 The Author(s).\n The Journal of Pathology<\/jats:italic>\n published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n <\/jats:p>","DOI":"10.1002\/path.70121","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:12:43Z","timestamp":1788945163000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential\n \n FGFR1<\/i>\n <\/scp>\n copy number status displays unique tumour immune microenvironment in triple\u2010negative breast cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4196-1700","authenticated-orcid":false,"given":"Yike","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pathology, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Medicine Amoy Diagnostics Co., Ltd. Xiamen PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianlin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medicine Amoy Diagnostics Co., Ltd. Xiamen PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changbin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medicine Amoy Diagnostics Co., Ltd. Xiamen PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2570-6280","authenticated-orcid":false,"given":"Shafei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4787-2925","authenticated-orcid":false,"given":"Zhiyong","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular Pathology Research Centre Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-024-06602-x","article-title":"Fibroblast growth receptor 1 is regulated by G\u2010quadruplex in metastatic breast cancer","volume":"7","author":"Lin H","year":"2024","journal-title":"Commun Biol"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nrc2780","article-title":"Fibroblast growth factor signalling: from development to cancer","volume":"10","author":"Turner N","year":"2010","journal-title":"Nat Rev Cancer"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"4564","DOI":"10.7150\/thno.68972","article-title":"FGFR blockade boosts T cell infiltration into triple\u2010negative breast cancer by regulating cancer\u2010associated fibroblasts","volume":"12","author":"Wu Y","year":"2022","journal-title":"Theranostics"},{"key":"e_1_2_8_5_1","first-page":"3893","article-title":"Comprehensive identification of FGFR1\u20104 alterations in 5 557 Chinese patients with solid tumors by next\u2010generation sequencing","volume":"11","author":"Gu W","year":"2021","journal-title":"Am J Cancer Res"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1158\/1078-0432.CCR-13-0190","article-title":"Targeting FGFR with dovitinib (TKI258): preclinical and clinical data in breast cancer","volume":"19","author":"Andr\u00e9 F","year":"2013","journal-title":"Clin Cancer Res"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1158\/0008-5472.CAN-09-3746","article-title":"FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer","volume":"70","author":"Turner N","year":"2010","journal-title":"Cancer Res"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2022.215867","article-title":"FGFR1\/MAPK\u2010directed brachyury activation drives PD\u2010L1\u2010mediated immune evasion to promote lung cancer progression","volume":"547","author":"Hu Y","year":"2022","journal-title":"Cancer Lett"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12943-023-01761-7","article-title":"Unleashing the potential of combining FGFR inhibitor and immune checkpoint blockade for FGF\/FGFR signaling in tumor microenvironment","volume":"22","author":"Ruan R","year":"2023","journal-title":"Mol Cancer"},{"key":"e_1_2_8_10_1","unstructured":"FGFR1 (8p11.2) Amplification FISH Tissue [Internet]. Mayo Clinic Laboratories. Test ID: FGF1F. [Accessed August 27 2026]: Available from:https:\/\/www.mayocliniclabs.com\/test-catalog\/Overview\/58124#Overview."},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","DOI":"10.1186\/bcr3239","article-title":"FGFR1 is amplified during the progression of in situ to invasive breast carcinoma","volume":"14","author":"Jang M","year":"2012","journal-title":"Breast Cancer Res"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","DOI":"10.1186\/1756-9966-31-103","article-title":"FGFR\u20101 amplification in metastatic lymph\u2010nodal and haematogenous lobular breast carcinoma","volume":"31","author":"Brunello E","year":"2012","journal-title":"J Exp Clin Cancer Res"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","DOI":"10.1186\/bcr1665","article-title":"FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis","volume":"9","author":"Elbauomy Elsheikh S","year":"2007","journal-title":"Breast Cancer 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H","year":"2021","journal-title":"NPJ Breast Cancer"},{"key":"e_1_2_8_38_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2203690","article-title":"Trastuzumab deruxtecan in previously treated HER2\u2010low advanced breast cancer","volume":"387","author":"Modi S","year":"2022","journal-title":"N Engl J Med"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1016\/j.cell.2023.01.040","article-title":"Deciphering breast cancer: from biology to the clinic","volume":"186","author":"Nolan E","year":"2023","journal-title":"Cell"}],"container-title":["The Journal of 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