{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,3,4]],"date-time":"2023-03-04T05:38:12Z","timestamp":1677908292001},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T00:00:00Z","timestamp":1661558400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T00:00:00Z","timestamp":1661558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Leipzig"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>The prospective multicenter VARIANZ study aimed to identify resistance biomarkers for HER2-targeted treatment in advanced gastric and esophago-gastric junction cancer (GC, EGJC). HER2 test deviations were found in 90 (22.3%) of 404 cases (central versus local testing) and were associated with negative impact on survival for trastuzumab-treated patients. Here, we investigated methodological and biological variables that may promote deviating HER2 test results.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We analyzed HER2 testing procedures and participation in quality assurance programs of 105\u00a0participating local pathology laboratories. Furthermore, tumor localization and histological subtypes were compared between patients with centrally confirmed (central\u00a0HER2\u2009+\u2009\/local\u00a0HER2\u2009+\u2009, <jats:italic>n<\/jats:italic>\u2009=\u200968) and unconfirmed HER2 status (central\u00a0HER2\u00a0\u2212\/local\u00a0HER2\u2009+\u2009, <jats:italic>n<\/jats:italic>\u2009=\u200968).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>For central HER2 testing, concordance between in situ hybridization (ISH) and immunohistochemistry (IHC) was 98.3%, with IHC sensitivity of 93.3% (84 IHC\u2009+\u2009of 90 ISH\u2009+), specificity of 99.5% (389 IHC- of 391 ISH-), and a positive diagnosis rate of 97.7%. Central confirmation of the local HER2 IHC scores were seen for the majority of locally HER2- IHC 0\/1 (172\/178; 96.6%), but less frequently for locally IHC3\u2009+\u2009(57\/124; 46.0%) cases. Deviation rate was not associated with IHC antibody platform used in the local pathology institute neither with participation in quality-assuring tests. Regarding tumor characteristics, deviating test results were more frequently found in GC vs. EGJC (69.1% vs. 39.7%; <jats:italic>p<\/jats:italic>\u2009=\u20090.001) and in Laur\u00e9n diffuse vs. intestinal subtype (23.5%\u00a0vs. 5.9%, <jats:italic>p<\/jats:italic>\u2009=\u20090.004).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Tumor localization and histological subtype have an impact on HER2 test deviation rates. Assessment of HER2 remains challenging for GC and EGJC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-022-04208-6","type":"journal-article","created":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T17:02:31Z","timestamp":1661619751000},"page":"1319-1329","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deviating HER2 test results in gastric cancer: analysis from the prospective multicenter VARIANZ study"],"prefix":"10.1007","volume":"149","author":[{"ORCID":"http:\/\/orcid.org\/0000-0001-5156-9211","authenticated-orcid":false,"given":"Katharina","family":"Kolbe","sequence":"first","affiliation":[]},{"ORCID":"http:\/\/orcid.org\/0000-0002-7814-0367","authenticated-orcid":false,"given":"Ivonne","family":"Haffner","sequence":"additional","affiliation":[]},{"ORCID":"http:\/\/orcid.org\/0000-0002-5188-5537","authenticated-orcid":false,"given":"Katrin","family":"Schierle","sequence":"additional","affiliation":[]},{"given":"Dieter","family":"Maier","sequence":"additional","affiliation":[]},{"given":"Birgitta","family":"Geier","sequence":"additional","affiliation":[]},{"ORCID":"http:\/\/orcid.org\/0000-0002-6900-0944","authenticated-orcid":false,"given":"Birgit","family":"Luber","sequence":"additional","affiliation":[]},{"given":"Hendrik","family":"Bl\u00e4ker","sequence":"additional","affiliation":[]},{"given":"Christian","family":"Wittekind","sequence":"additional","affiliation":[]},{"ORCID":"http:\/\/orcid.org\/0000-0001-8591-9339","authenticated-orcid":false,"given":"Florian","family":"Lordick","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,8,27]]},"reference":[{"key":"4208_CR1","doi-asserted-by":"publisher","first-page":"6438","DOI":"10.3748\/wjg.v19.i38.6438","volume":"19","author":"LF Abrah\u00e3o-Machado","year":"2013","unstructured":"Abrah\u00e3o-Machado LF, J\u00e1come AAdA, Wohnrath DR, dos Santos JS, Carneseca EC, Fregnani JHTG, Scapulatempo-Neto C (2013) HER2 in gastric cancer: comparative analysis of three different antibodies using whole-tissue sections and tissue microarrays. 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