{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:32:47Z","timestamp":1783629167597,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009564","name":"Health and Family Planning Commission of Sichuan Province","doi-asserted-by":"publisher","award":["2018ZHYL0213"],"award-info":[{"award-number":["2018ZHYL0213"]}],"id":[{"id":"10.13039\/501100009564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study aimed to present a comprehensive assessment of anaplastic lymphoma kinase (<jats:italic>ALK<\/jats:italic>) rearrangements evaluated by DNA\/RNA\u2010based next\u2010generation sequencing (NGS) and Ventana immunohistochemistry (IHC) in patients with non\u2010small\u2010cell lung cancer (NSCLC) and to evaluate the therapeutic outcomes of ALK tyrosine kinase inhibitor (TKI) treatment. We investigated <jats:italic>ALK<\/jats:italic> gene fusions in 14,894 patients with NSCLC using Ventana IHC and NGS, including 12,533 cases detected via DNA\u2010based NGS and 2,361 cases using RNA\u2010based NGS. The overall percentage agreement (OPA), positive percentage agreement (PPA), and negative percentage agreement (NPA) were calculated when comparing the results between NGS and IHC. The therapeutic responses to ALK\u2010TKIs were also evaluated. In total, 3.50% (439\/12,533) of specimens were NGS ALK\u2010positive (NGS\u2010p) in the DNA\u2010based NGS cohort and 3.63% (455\/12,533) were IHC ALK\u2010positive (IHC\u2010p). The OPA of NGS was 99.60%, whereas its PPA and NPA were 92.75 and 99.86%, respectively. In the adenocarcinoma (ADC) subcohort, the PPA was 95.69%. In the RNA\u2010based NGS cohort, 2.20% (52\/2,361) of specimens were NGS\u2010p and 2.63% (62\/2,361) were IHC\u2010p. The OPA of NGS was 99.49%; its PPA and NPA were 82.26 and 99.96%, respectively. Thirteen patients with discordant results received ALK\u2010TKI treatment. In the seven NGS\u2010p\/IHC\u2010negative (IHC\u2010n) patients, the overall response rate (ORR) was 85.4% (6\/7) and the disease control rate (DCR) was 100%. In the six NGS\u2010negative\/IHC\u2010p patients, the ORR was 66.7% (4\/6) and the DCR was 100%. In summary, a high concordance of <jats:italic>ALK<\/jats:italic> gene fusion detected via NGS and IHC was observed in this study. DNA\u2010based NGS had a higher OPA, PPA, and PPA in the ADC subcohort, whereas RNA\u2010based NGS had a higher NPA. Overall, the results suggest that the combination of NGS and IHC can improve the accuracy of <jats:italic>ALK<\/jats:italic> fusion detection; hence, a result determination algorithm for clinical detection of <jats:italic>ALK<\/jats:italic> gene fusion was also proposed.<\/jats:p>","DOI":"10.1002\/cjp2.289","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T08:10:11Z","timestamp":1658131811000},"page":"538-549","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification and therapeutic evaluation of <scp><i>ALK<\/i><\/scp> rearrangements in non\u2010small\u2010cell lung cancer"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3417-0468","authenticated-orcid":false,"given":"Ruiying","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pathology, Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianying","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary, Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5227-1940","authenticated-orcid":false,"given":"Jikai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinchen","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2548-5492","authenticated-orcid":false,"given":"Yuchen","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.11.033"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-1123"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2011.159467"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.65.8732"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-3260"},{"key":"e_1_2_8_7_1","first-page":"147","article-title":"ALK (D5F3) CDx: an immunohistochemistry assay to 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