{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T07:43:18Z","timestamp":1773387798240,"version":"3.50.1"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>Systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a group of heterogenous CD30<jats:sup>+<\/jats:sup> T-cell non-Hodgkin lymphomas. Previous studies have highlighted the importance of JAK\/STAT3 signaling activation in the molecular pathogenesis of ALK<jats:sup>\u2212<\/jats:sup> ALCLs. In the present study, we aimed to establish a potential relationship between JAK\/STAT3 signaling activation and clinicopathologic features in ALK<jats:sup>\u2212<\/jats:sup> ALCLs, and further recognize the heterogenous nature of these neoplasms. Immunohistochemistry staining of the phosphorylated-STAT3 (p-STAT3) and dual-specificity protein phosphatase 22 (<jats:italic toggle=\"yes\">DUSP22<\/jats:italic>) gene rearrangement analysis were performed. Forty-five cases of ALK<jats:sup>\u2212<\/jats:sup> ALCL were divided into 3 groups, including 9 <jats:italic toggle=\"yes\">DUSP22<\/jats:italic>-rearranged ALCLs, 21 p-STAT3<jats:sup>+<\/jats:sup> double-negative (DN) ALCLs (both <jats:italic toggle=\"yes\">ALK<\/jats:italic> and <jats:italic toggle=\"yes\">DUSP22<\/jats:italic> rearrangement negative), and 15 p-STAT3<jats:sup>\u2212<\/jats:sup> DN-ALCLs. Morphologically, p-STAT3<jats:sup>+<\/jats:sup> DN-ALCLs exhibited sheet-like neoplastic cells and sometimes showed large pleomorphic cells scattered in a lymphocyte-rich background more frequently than those in other ALK<jats:sup>\u2212<\/jats:sup> ALCLs subtypes. Phenotypically, the p-STAT3<jats:sup>+<\/jats:sup> DN-ALCLs frequently expressed cytotoxic molecules, epithelial membrane antigen, and programmed death-ligand 1, whereas CD3 and CD5 expression was not observed. Clinically, patients with p-STAT3<jats:sup>+<\/jats:sup> DN-ALCLs had a better prognosis than those with p-STAT3<jats:sup>\u2212<\/jats:sup> DN-ALCLs. These observations suggest that p-STAT3<jats:sup>+<\/jats:sup> DN-ALCLs represent a distinct subtype of ALK<jats:sup>\u2212<\/jats:sup> ALCLs. Identifying ALK<jats:sup>\u2212<\/jats:sup> ALCL subtypes by using p-STAT3 staining and <jats:italic toggle=\"yes\">DUSP22<\/jats:italic> rearrangement is a promising approach that may contribute to risk stratification and better treatment decisions in the future clinical practice.<\/jats:p>","DOI":"10.1097\/pas.0000000000001995","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T19:11:31Z","timestamp":1667243491000},"page":"55-64","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":10,"title":["JAK\/STAT3 Signaling Activation Related to Distinct Clinicopathologic Features in Systemic ALK\u2212 Anaplastic Large Cell Lymphomas"],"prefix":"10.1097","volume":"47","author":[{"given":"Jian-chao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-hua","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-qing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-feng","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi Province"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue-ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-feng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-ping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"R2-20250608","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1182\/blood-2014-04-571091","article-title":"ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical 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