{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:37:45Z","timestamp":1770824265685,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T00:00:00Z","timestamp":1602460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The American Society of Clinical Oncology\/College of American Pathologists (ASCO\/CAP) updated the testing guideline in 2018 to address issues arising from uncommon human epidermal growth factor receptor 2 (<jats:italic>HER2<\/jats:italic>) fluorescence <jats:italic>in\u2010situ<\/jats:italic> hybridisation (FISH) results according to the 2013 guideline. Next\u2010generation sequencing (NGS) may be used to better classify patients. The aim of this study was to assess the <jats:italic>ERBB2<\/jats:italic> amplification status of invasive breast carcinoma with equivocal HER2 immunohistochemistry (IHC) results by using NGS, focusing on Group 4 (<jats:italic>HER2<\/jats:italic>\/CEP17 ratio of &lt;2.0; average <jats:italic>HER2<\/jats:italic> signals\/cell of \u22654.0 and &lt;6.0).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We retrospectively reviewed <jats:italic>HER2<\/jats:italic> FISH and NGS data of HER2 IHC\u2010equivocal breast carcinomas at our centre between January 2009 and September 2019, wherein all three assays were performed on the same tissue block, and compared <jats:italic>HER2<\/jats:italic> FISH results, according to the 2018 ASCO\/CAP guideline, and the <jats:italic>ERBB2<\/jats:italic> amplification status determined with NGS. A total of 52 <jats:italic>HER2<\/jats:italic> FISH and NGS results from 51 patients with HER2 IHC\u2010equivocal breast carcinomas were reviewed. The cohort included eight cases classified as 2018 ASCO\/CAP <jats:italic>in\u2010situ<\/jats:italic> hybridisation Group 1, three classified as Group 2, three classified as Group 3, 14 classified as Group 4, and 24 classified as Group 5. Thirteen of 14 (92.9%) Group 4 (<jats:italic>HER2<\/jats:italic>\u2010negative) cases were classified as <jats:italic>ERBB2<\/jats:italic>\u2010non\u2010amplified by the use of NGS; the discordant case was later classified as Group 1 with alternative sample FISH testing. NGS revealed no significant difference in somatic mutations or copy number alterations between Groups 4 and 5.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our NGS findings support the reclassification of <jats:italic>HER2<\/jats:italic> FISH\u2010equivocal cases as <jats:italic>HER2<\/jats:italic>\u2010negative under the 2018 ASCO\/CAP guideline.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14241","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T07:31:35Z","timestamp":1598427095000},"page":"498-507","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Next\u2010generation assessment of human epidermal growth factor receptor 2 gene (<i>ERBB2<\/i>) amplification status in invasive breast carcinoma: a focus on Group 4 by use of the 2018 American Society of Clinical Oncology\/College of American Pathologists HER2 testing guideline"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6316-1819","authenticated-orcid":false,"given":"Raza S","family":"Hoda","sequence":"first","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita S","family":"Bowman","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet","family":"Zehir","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedram","family":"Razavi","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center New York NY 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