{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T19:43:38Z","timestamp":1774986218794,"version":"3.50.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"S1","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pathologe"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1007\/s00292-020-00878-6","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T10:03:26Z","timestamp":1608545006000},"page":"62-68","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["ISH-based HER2 diagnostics","ISH-basierte HER2-Diagnostik"],"prefix":"10.1007","volume":"42","author":[{"given":"Josef","family":"R\u00fcschoff","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Nagelmeier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bharat","family":"Jasani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Stoss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,12,21]]},"reference":[{"key":"878_CR1","unstructured":"FDA HER2-Testbestimmungen: Packungsbeilage der jeweiligen Assays (z.\u202fB. PathVision HER\u20112 DANN PROBE KIT https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfpma\/pma.cfm?id=p980024. Zugegriffen: 30.\u00a0Sept. 2020)"},{"issue":"1","key":"878_CR2","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s00428-007-0424-5","volume":"451","author":"M Dietel","year":"2007","unstructured":"Dietel\u00a0M, Ellis\u00a0IO, H\u00f6fler\u00a0H et\u00a0al (2007) Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of American Pathologists. Virchows Arch 451(1):19\u201325","journal-title":"Virchows Arch"},{"issue":"6","key":"878_CR3","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1097\/PAS.0b013e3181d96231","volume":"34","author":"BG Papouchado","year":"2010","unstructured":"Papouchado\u00a0BG, Myles\u00a0J, Lloyd\u00a0RV et\u00a0al (2010) Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: comparison with FISH and assessment of interobserver reproducibility. Am J Surg Pathol 34(6):767\u2013776","journal-title":"Am J Surg Pathol"},{"issue":"7","key":"878_CR4","doi-asserted-by":"publisher","first-page":"2033","DOI":"10.1158\/1078-0432.CCR-18-2275","volume":"25","author":"F Meric-Bernstam","year":"2019","unstructured":"Meric-Bernstam\u00a0F, Johnson\u00a0AM, Dumbrava\u00a0EEI et al (2019) Advances in HER2-targeted therapy: novel agents and opportunities beyond breast and gastric cancer. Clin Cancer Res 25(7):2033\u20132041","journal-title":"Clin Cancer Res"},{"key":"878_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1634\/theoncologist.2018-0845","volume":"24","author":"J Subramanian","year":"2019","unstructured":"Subramanian\u00a0J et\u00a0al (2019) Emergence of ERBB2 mutation as a\u00a0biomarker and an actionable target in solid cancers. Oncologist 24:1\u201312","journal-title":"Oncologist"},{"issue":"1","key":"878_CR6","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1200\/JCO.2006.09.2775","volume":"25","author":"AC Wolff","year":"2007","unstructured":"Wolff\u00a0AC, Hammond\u00a0ME, Schwartz\u00a0JN et\u00a0al (2007) American Society of Clinical Oncology\/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J\u00a0Clin Oncol 25(1):118\u2013145","journal-title":"J Clin Oncol"},{"issue":"31","key":"878_CR7","doi-asserted-by":"publisher","first-page":"3997","DOI":"10.1200\/JCO.2013.50.9984","volume":"31","author":"AC Wolff","year":"2013","unstructured":"Wolff\u00a0AC, Hammond\u00a0ME, Hicks\u00a0DG et\u00a0al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology\/College of American Pathologists clinical practice guideline update. J\u00a0Clin Oncol 31(31):3997\u20134013","journal-title":"J Clin Oncol"},{"issue":"20","key":"878_CR8","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1200\/JCO.2018.77.8738","volume":"36","author":"AC Wolff","year":"2018","unstructured":"Wolff\u00a0AC, Hammond\u00a0MEH, Allison\u00a0KH et\u00a0al (2018) Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology\/College of American Pathologists Clinical Practice Guideline Focused Update. J\u00a0Clin Oncol 36(20):2105\u20132122","journal-title":"J Clin Oncol"},{"issue":"8","key":"878_CR9","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1200\/JCO.2007.14.8197","volume":"27","author":"G Sauter","year":"2009","unstructured":"Sauter\u00a0G, Lee\u00a0J, Bartlett\u00a0JM, Slamon\u00a0DJ, Press\u00a0MF (2009) Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J\u00a0Clin Oncol 27(8):1323\u20131333","journal-title":"J Clin Oncol"},{"issue":"2","key":"878_CR10","doi-asserted-by":"publisher","first-page":"45","DOI":"10.4103\/2278-330X.208841","volume":"6","author":"MK Panigrahi","year":"2017","unstructured":"Panigrahi\u00a0MK, Kumar\u00a0D, Mehta\u00a0A, Saikia\u00a0KK (2017) Outcome of HER2 Testing by FISH applying ASCO\/CAP 2007 and 2013 guideline in IHC equivocal group of breast cancer: experience at tertiary cancer care centre. South Asian J Cancer 6(2):45\u201346","journal-title":"South Asian J Cancer"},{"issue":"2","key":"878_CR11","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s00428-015-1871-z","volume":"468","author":"N Tchrakian","year":"2016","unstructured":"Tchrakian\u00a0N, Flanagan\u00a0L, Harford\u00a0J, Gannon\u00a0JM, Quinn\u00a0CM (2016) New ASCO\/CAP guideline recommendations for HER2 testing increase the proportion of reflex in situ hybridization tests and of HER2 positive breast cancers. Virchows Arch 468(2):207\u2013211","journal-title":"Virchows Arch"},{"issue":"17","key":"878_CR12","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1200\/JCO.19.02488","volume":"38","author":"P Tarantino","year":"2020","unstructured":"Tarantino\u00a0P, Hamilton\u00a0E, Tolaney\u00a0SM et al (2020) HER2-low breast cancer: pathological and clinical landscape. J\u00a0Clin Oncol 38(17):1951\u20131962","journal-title":"J Clin Oncol"},{"key":"878_CR13","unstructured":"AWMF S3 Leitlinie Mammakarzinom (Langversion 4.3 \u2013 Februar 2020), https:\/\/www.awmf.org\/uploads\/tx_szleitlinien\/032-045OLl_S3_Mammakarzinom_2020-02.pdf"},{"issue":"2","key":"878_CR14","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s00292-019-0578-3","volume":"40","author":"A Lebeau","year":"2019","unstructured":"Lebeau\u00a0A, Denkert\u00a0C, Sinn\u00a0P, Schmidt\u00a0M, W\u00f6ckel\u00a0A (2019) Update der S3-Leitlinie Mammakarzinom: Was gibt es Neues f\u00fcr Pathologen? Pathologe 40(2):185\u2013198","journal-title":"Pathologe"},{"issue":"12","key":"878_CR15","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1038\/modpathol.2015.112","volume":"28","author":"OC Stoss","year":"2015","unstructured":"Stoss\u00a0OC, Scheel\u00a0A, Nagelmeier\u00a0I et al (2015) Impact of updated HER2 testing guidelines in breast cancer\u2014re-evaluation of HERA trial fluorescence in situ hybridization data. Mod Pathol 28(12):1528\u20131534","journal-title":"Mod Pathol"},{"issue":"4","key":"878_CR16","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1200\/JCO.2016.69.4836","volume":"35","author":"AN Bartley","year":"2017","unstructured":"Bartley\u00a0AN, Washington\u00a0MK, Colasacco\u00a0C et\u00a0al (2017) HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J\u00a0Clin Oncol 35(4):446\u2013464","journal-title":"J Clin Oncol"},{"issue":"9742","key":"878_CR17","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/S0140-6736(10)61121-X","volume":"376","author":"YJ Bang","year":"2010","unstructured":"Bang\u00a0YJ, Van Cutsem\u00a0E, Feyereislova\u00a0A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a\u00a0phase 3, open-label, randomised controlled trial [published correction appears in Lancet. 2010 Oct 16;376(9749):1302]. Lancet 376(9742):687\u2013697","journal-title":"Lancet"},{"issue":"7","key":"878_CR18","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1111\/j.1365-2559.2008.03028.x","volume":"52","author":"M Hofmann","year":"2008","unstructured":"Hofmann\u00a0M, Stoss\u00a0O, Shi\u00a0D et\u00a0al (2008) Assessment of a\u00a0HER2 scoring system for gastric cancer: results from a\u00a0validation study. Histopathology 52(7):797\u2013805","journal-title":"Histopathology"},{"issue":"5","key":"878_CR19","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/modpathol.2011.198","volume":"25","author":"J R\u00fcschoff","year":"2012","unstructured":"R\u00fcschoff\u00a0J, Hanna\u00a0W, Bilous\u00a0M et\u00a0al (2012) HER2 testing in gastric cancer: a\u00a0practical approach. Mod Pathol 25(5):637\u2013650","journal-title":"Mod Pathol"},{"issue":"4","key":"878_CR20","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s00292-016-0179-3","volume":"37","author":"G Baretton","year":"2016","unstructured":"Baretton\u00a0G, Dietel\u00a0M, Gaiser\u00a0T et al (2016) HER2-Testung beim Magenkarzinom : Ergebnisse eines deutschen Expertentreffens [HER2 testing in gastric cancer : results of a\u00a0meeting of German experts]. Pathologe 37(4):361\u2013366","journal-title":"Pathologe"},{"issue":"5","key":"878_CR21","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s00428-019-02541-9","volume":"474","author":"G Baretton","year":"2019","unstructured":"Baretton\u00a0G, Kreipe\u00a0HH, Schirmacher\u00a0P et al (2019) HER2 testing in gastric cancer diagnosis: insights on variables influencing HER2-positivity from a\u00a0large, multicenter, observational study in Germany. Virchows Arch 474(5):551\u2013560","journal-title":"Virchows Arch"},{"issue":"1","key":"878_CR22","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13000-018-0696-x","volume":"13","author":"AH Scheel","year":"2018","unstructured":"Scheel\u00a0AH, Penault-Llorca\u00a0F, Hanna\u00a0W et al (2018) Physical basis of the \u2018magnification rule\u2019 for standardized Immunohistochemical scoring of HER2 in breast and gastric cancer. Diagn Pathol 13(1):19","journal-title":"Diagn Pathol"},{"issue":"3","key":"878_CR23","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1007\/s10120-014-0402-y","volume":"18","author":"E Van Cutsem","year":"2015","unstructured":"Van Cutsem\u00a0E, Bang\u00a0YJ, Feng-Yi\u00a0F et al (2015) HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer 18(3):476\u2013484","journal-title":"Gastric Cancer"},{"issue":"10","key":"878_CR24","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1016\/S1470-2045(18)30481-9","volume":"19","author":"J Tabernero","year":"2018","unstructured":"Tabernero\u00a0J, Hoff\u00a0PM, Shen\u00a0L et al (2018) Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a\u00a0double-blind, randomised, placebo-controlled phase 3\u00a0study. Lancet Oncol 19(10):1372\u20131384","journal-title":"Lancet Oncol"},{"issue":"4","key":"878_CR25","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1007\/s10120-018-00923-7","volume":"22","author":"MA Shah","year":"2019","unstructured":"Shah\u00a0MA, Kang\u00a0YK, Thuss-Patience\u00a0PC et al (2019) Biomarker analysis of the GATSBY study of trastuzumab emtansine versus a\u00a0taxane in previously treated HER2-positive advanced gastric\/gastroesophageal junction cancer. Gastric Cancer 22(4):803\u2013816","journal-title":"Gastric Cancer"},{"issue":"2","key":"878_CR26","doi-asserted-by":"publisher","first-page":"103","DOI":"10.4132\/jptm.2017.01.24","volume":"51","author":"HS Lee","year":"2017","unstructured":"Lee\u00a0HS, Kim\u00a0WH, Kwak\u00a0Y et\u00a0al (2017) Molecular testing for gastrointestinal cancer. J\u00a0Pathol Transl Med 51(2):103\u2013121","journal-title":"J Pathol Transl Med"},{"issue":"1","key":"878_CR27","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12957-016-0792-x","volume":"14","author":"X Li","year":"2016","unstructured":"Li\u00a0X, Zhao\u00a0H, Gu\u00a0J, Zheng\u00a0L (2016) Prognostic role of HER2 amplification based on fluorescence in situ hybridization (FISH) in pancreatic ductal adenocarcinoma (PDAC): a\u00a0meta-analysis. World J Surg Oncol 14(1):38","journal-title":"World J Surg Oncol"},{"issue":"6","key":"878_CR28","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/S1470-2045(16)00150-9","volume":"17","author":"A Sartore-Bianchi","year":"2016","unstructured":"Sartore-Bianchi\u00a0A, Trusolino\u00a0L, Martino\u00a0C et al (2016) Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12\/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a\u00a0proof-of-concept, multicentre, open-label, phase 2 trial [published correction appears in Lancet Oncol. 2016 Oct;17 (10 ):e420]. Lancet Oncol 17(6):738\u2013746","journal-title":"Lancet Oncol"},{"issue":"11","key":"878_CR29","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1038\/modpathol.2015.98","volume":"28","author":"E Valtorta","year":"2015","unstructured":"Valtorta\u00a0E, Martino\u00a0C, Sartore-Bianchi\u00a0A et al (2015) Assessment of a\u00a0HER2 scoring system for colorectal cancer: results from a\u00a0validation study. Mod Pathol 28(11):1481\u20131491","journal-title":"Mod Pathol"},{"issue":"4","key":"878_CR30","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1002\/path.4679","volume":"238","author":"SD Richman","year":"2016","unstructured":"Richman\u00a0SD, Southward\u00a0K, Chambers\u00a0P et\u00a0al (2016) HER2 overexpression and amplification as a\u00a0potential therapeutic target in colorectal cancer: analysis of 3256\u00a0patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials. J\u00a0Pathol 238(4):562\u2013570","journal-title":"J Pathol"},{"issue":"4","key":"878_CR31","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s00428-015-1898-1","volume":"468","author":"H Yoshida","year":"2016","unstructured":"Yoshida\u00a0H, Shimada\u00a0K, Kosuge\u00a0T, Hiraoka\u00a0N (2016) A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status. Virchows Arch 468(4):431\u2013439","journal-title":"Virchows Arch"},{"issue":"4","key":"878_CR32","doi-asserted-by":"publisher","first-page":"e0153533","DOI":"10.1371\/journal.pone.0153533","volume":"11","author":"J Elebro","year":"2016","unstructured":"Elebro\u00a0J, Heby\u00a0M, Warfvinge\u00a0CF, Nodin\u00a0B, Eberhard\u00a0J, Jirstr\u00f6m\u00a0K (2016) Expression and prognostic significance of human epidermal growth factor receptors 1, 2 and 3 in periampullary adenocarcinoma. Plos One 11(4):e153533","journal-title":"Plos One"},{"issue":"1","key":"878_CR33","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s10555-016-9645-x","volume":"36","author":"S Galdy","year":"2017","unstructured":"Galdy\u00a0S, Lamarca\u00a0A, McNamara\u00a0MG et al (2017) HER2\/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a\u00a0potential therapeutic target? Cancer Metastasis Rev 36(1):141\u2013157","journal-title":"Cancer Metastasis Rev"},{"issue":"6","key":"878_CR34","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1136\/jclinpath-2019-206204","volume":"73","author":"K Hotta","year":"2020","unstructured":"Hotta\u00a0K, Yanai\u00a0H, Ohashi\u00a0K et al (2020) Pilot evaluation of a\u00a0HER2 testing in non-small-cell lung cancer. J\u00a0Clin Pathol 73(6):353\u2013357","journal-title":"J Clin Pathol"},{"issue":"5","key":"878_CR35","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1111\/bju.15006","volume":"125","author":"RW Madison","year":"2020","unstructured":"Madison\u00a0RW, Gupta\u00a0SV, Elamin\u00a0YY et\u00a0al (2020) Urothelial cancer harbours EGFR and HER2 amplifications and exon 20 insertions. BJU Int 125(5):739\u2013746","journal-title":"BJU Int"},{"key":"878_CR36","unstructured":"https:\/\/www.mycancergenome.org\/content\/alteration\/erbb2-mutation\/#ref-4. Zugegriffen: 30.\u00a0Sept. 2020"},{"issue":"8","key":"878_CR37","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1158\/2159-8290.CD-17-0151","volume":"7","author":"AACR Project GENIE Consortium","year":"2017","unstructured":"AACR Project GENIE Consortium (2017) AACR project GENIE: powering precision medicine through an international consortium. Cancer Discov 7(8):818\u2013831","journal-title":"Cancer Discov"}],"container-title":["Der Pathologe"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00292-020-00878-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00292-020-00878-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00292-020-00878-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T12:03:17Z","timestamp":1636113797000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00292-020-00878-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,21]]},"references-count":37,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["878"],"URL":"https:\/\/doi.org\/10.1007\/s00292-020-00878-6","relation":{},"ISSN":["0172-8113","1432-1963"],"issn-type":[{"value":"0172-8113","type":"print"},{"value":"1432-1963","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,21]]},"assertion":[{"value":"20 November 2020","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2020","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical guidelines"}},{"value":"J.\u00a0R\u00fcschoff is co-founder of Targos GmbH, Germany. I.\u00a0Nagelmeier, B.\u00a0Jasani, and O.\u00a0Stoss declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}