{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T05:44:43Z","timestamp":1791783883647,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23\u2009K27385"],"award-info":[{"award-number":["23\u2009K27385"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Although collagen type 1 alpha 1 (\n                    <jats:italic>COL1A1<\/jats:italic>\n                    )\u2013platelet\u2010derived growth factor B\u2010chain (\n                    <jats:italic>PDGFB<\/jats:italic>\n                    ) gene fusion is a characteristic driver alteration in fibrosarcomatous dermatofibrosarcoma protuberans (FS\u2010DFSP), an aggressive DFSP variant, the tumor microenvironment (TME) underlying the aggressive phenotype remains unclear. We investigated microenvironmental and molecular differences between pure\u2010DFSP and FS\u2010DFSP using integrated histopathologic and transcriptomic analyses of archival samples from 122 patients, including 39 with FS\u2010DFSP. Histopathologic evaluation, immunohistochemistry, and transcriptomic analyses were performed to assess vascular features, cancer\u2010associated fibroblasts (CAFs), macrophage infiltration, and angiogenesis\u2010related molecular alterations. FS\u2010DFSP demonstrated increased CD31\u2010positive vascular structures without a corresponding increase in \u03b1SMA\u2010positive vascular structures, suggesting immature vascular features. CAF markers, including periostin and fibroblast activation protein, were significantly upregulated in intratumoral and invasive front regions of FS\u2010DFSP. Gene expression analysis was performed separately for the fibrosarcomatous and DFSP components of the FS\u2010DFSP cases and for the pure\u2010DFSP cases. By targeted transcriptomic profiling, the DFSP and fibrosarcomatous components within the FS\u2010DFSP cases shared molecular features, suggesting early tumor microenvironment\u2010associated alterations that preceded overt fibrosarcomatous morphology. Integrated transcriptomic and protein analyses revealed upregulation of angiogenesis\u2010related molecules, including vascular endothelial growth factor A (VEGFA), C\u2010C motif chemokine ligand 2 (CCL2), and C\u2010X\u2010C motif chemokine receptor 4 (CXCR4) in FS\u2010DFSP. Periostin\u2010positive CAFs coexpressed VEGFA and CCL2, potentially contributing to angiogenic features within the tumor microenvironment. These findings reveal that FS\u2010DFSP is characterized by coordinated angiogenic and stromal remodeling involving tumor cells and CAFs and suggest that the tumor microenvironment may represent a potential focus for future therapeutic investigation.\n                  <\/jats:p>","DOI":"10.1111\/cas.70558","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:48:39Z","timestamp":1791780519000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Angiogenic and Stromal Remodeling Associated With Aggressive Fibrosarcomatous Dermatofibrosarcoma Protuberans"],"prefix":"10.1111","author":[{"given":"Sakura","family":"Shiraishi","sequence":"first","affiliation":[{"name":"Department of Anatomic Pathology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"},{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Takigawa","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohta","family":"Miyawaki","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Tomonaga","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7956-2190","authenticated-orcid":false,"given":"Makoto","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5815-4585","authenticated-orcid":false,"given":"Koji","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuharu","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9636-1182","authenticated-orcid":false,"given":"Yoshinao","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"key":"e_1_2_13_2_1","volume-title":"Soft Tissue and Bone Tumours","author":"WHO Classification of Tumours Editorial Board","year":"2020"},{"issue":"1","key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/ng0197-95","article-title":"Deregulation of the Platelet\u2010Derived Growth Factor B\u2010Chain Gene via Fusion With Collagen Gene COL1A1 in Dermatofibrosarcoma Protuberans and Giant\u2010Cell Fibroblastoma","volume":"15","author":"Simon M. 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