{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:17:16Z","timestamp":1787854636778,"version":"build-2784847793"},"reference-count":29,"publisher":"BMJ","funder":[{"name":"National High Level Hospital Clinical Research Funding","award":["82504142"],"award-info":[{"award-number":["82504142"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["80102022504"],"award-info":[{"award-number":["80102022504"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2026,8,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Anaplastic lymphoma kinase (ALK) is implicated in ALK fusion-positive non-small cell lung cancer and inflammatory myofibroblastic tumours. Based on prior studies and our observations, ALK overexpression appears to be associated with FET (\n                      <jats:italic>FUS<\/jats:italic>\n                      \/\n                      <jats:italic>EWSR1<\/jats:italic>\n                      \/\n                      <jats:italic>TAF15<\/jats:italic>\n                      ) family rearrangements (\n                      <jats:italic>EWSR1<\/jats:italic>\n                      and\n                      <jats:italic>FUS<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we analysed 119 FET-rearranged tumours spanning 20 tumour types. Using ALK D5F3 immunohistochemistry (IHC), ALK overexpression was defined as positive only for scores of 2+ or 3+. Cases with ALK overexpression by IHC were further confirmed to lack ALK gene rearrangements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the cases, 28.6% (34\/119) demonstrated ALK overexpression (\u22652+). 9 disease types displayed ALK overexpression (\u22652+), including soft tissue sarcomas and salivary gland carcinomas. Notably, Ewing sarcoma had the highest ALK overexpression rate (51%, 22\/43). Both analysed clear cell sarcoma-like tumour of the gastrointestinal tract (GNET) cases (2\/2) were strongly positive (3+), while extraskeletal myxoid chondrosarcoma exhibited a high overexpression rate (50%, 2\/4). Additionally, angiomatoid fibrous histiocytoma showed moderate staining (75%, 3\/4, 2+). The other tumours with ALK overexpression were pulmonary myoepithelial carcinoma (1\/1),\n                      <jats:italic>EWSR1<\/jats:italic>\n                      -rearranged rhabdomyosarcoma (1\/1), desmoplastic small round cell tumour (25%, 1\/4), clear cell sarcoma of soft tissue (7.7%, 1\/13) and myxoid liposarcoma (6.7%, 1\/15). ALK overexpression (IHC\u22652+) occurred in both\n                      <jats:italic>EWSR1<\/jats:italic>\n                      -rearranged and\n                      <jats:italic>FUS<\/jats:italic>\n                      -rearranged tumours. Among fusion partners,\n                      <jats:italic>FLI1<\/jats:italic>\n                      -rearranged cases had the strongest ALK overexpression (70%, 7\/10).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings demonstrate that ALK overexpression is frequent in FET-rearranged tumours, warranting caution to avoid misdiagnosis, while also presenting potential therapeutic opportunities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jcp-2026-210760","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:20:26Z","timestamp":1787851226000},"page":"jcp-2026-210760","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["ALK overexpression without rearrangement widely exists in\n                    <i>EWSR1<\/i>\n                    \/\n                    <i>FUS<\/i>\n                    -rearranged soft tissue tumours"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-9870","authenticated-orcid":false,"given":"Lihong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 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