{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T16:53:27Z","timestamp":1783097607559,"version":"3.54.6"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017590","name":"Universit\u00e4tsklinikum Essen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In breast cancer (BC), overexpression of HER2 on the primary tumor (PT) is determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) to stratify samples as negative, equivocal and positive to identify patients (pts) for anti-HER2 therapy. CAP\/ASCO guidelines recommend FISH for analyzing\n                      <jats:italic>HER2\/neu<\/jats:italic>\n                      (\n                      <jats:italic>ERBB2<\/jats:italic>\n                      ) gene amplification and for resolving equivocal HER2 IHC results. However, pre-analytical and analytical aspects are often confounded by sample related limitations and tumor heterogeneity and HER2 expression may differ between the PT and circulating tumor cells (CTCs), the precursors of metastasis. We used a validation cohort of BC patients to establish a new DEPArray\u2122-PT-HER2-FISH workflow for further application in a development cohort, characterized as PT-HER2-negative but CTC-HER2\/\n                      <jats:italic>neu<\/jats:italic>\n                      -positive, to identify patients with PT-HER2 amplified cells not detected by routine pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      50\u00a0\u00b5m FFPE tumor curls from the validation cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200949) and the development cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200925) underwent cutting, deparaffinization and antigen retrieval followed by dissociation into a single-cell suspension. After staining for cytokeratin, vimentin, DAPI and separation via DEPArray\u2122, single cells were processed for HER2-FISH analysis to assess the number of chromosome 17 and HER2 loci signals for comparison, either with available IHC or conventional tissue section FISH. CTC-HER2\/\n                      <jats:italic>neu<\/jats:italic>\n                      status was determined using the AdnaTest\n                      <jats:italic>BreastCancer<\/jats:italic>\n                      (QIAGEN, Hilden, Germany)\n                      <jats:italic>.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Applying CAP\/ASCO guidelines for HER2 evaluation of single PT cells, the comparison of routine pathology and DEPArray\u2122-HER2-FISH analysis resulted in a concordance rate of 81.6% (40\/49 pts) in the validation cohort and 84% (21\/25 pts) in the development cohort, respectively. In the latter one, 4\/25 patients had single HER2-positive tumor cells with 2\/25 BC patients proven to be HER2-positive, despite being HER2-negative in routine pathology. The two other patients showed an equivocal HER2 status in the DEPArray\u2122-HER2-FISH workflow but a negative result in routine pathology. Whereas all four patients with discordant HER2 results had already died, 17\/21 patients with concordant HER2 results are still alive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The DEPArray\u2122 system allows pure tumor cell recovery for subsequent\n                      <jats:italic>HER2\/neu<\/jats:italic>\n                      FISH analysis and is highly concordant with conventional pathology. For PT-HER2-negative patients, harboring HER2\/\n                      <jats:italic>neu-<\/jats:italic>\n                      positive CTCs, this approach might allow caregivers to more effectively offer anti-HER2 treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12282-022-01330-8","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T03:03:31Z","timestamp":1642043011000},"page":"487-497","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Single HER2-positive tumor cells are detected in initially HER2-negative breast carcinomas using the DEPArray\u2122\u2013HER2-FISH workflow"],"prefix":"10.1007","volume":"29","author":[{"given":"Lisa","family":"Gr\u00fcntkemeier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Khurana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farideh Zamaniyan","family":"Bischoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Kimmig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Cotter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8081-1799","authenticated-orcid":false,"given":"Sabine","family":"Kasimir-Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"1330_CR1","unstructured":"Prognostic and Predictive Factors. https:\/\/www.ago-online.de\/fileadmin\/ago-online\/downloads\/_leitlinien\/kommission_mamma\/2021\/englisch\/_ohne_Literartur\/2021E_05_Prognostic_and_Predictive_Factors_MASTER_final_20210302.pdf]"},{"key":"1330_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/nature20785","author":"H Hosseini","year":"2016","unstructured":"Hosseini H, Obradovic MMS, Hoffmann M, Harper KL, Sosa MS, Werner-Klein M, Nanduri LK, Werno C, Ehrl C, Maneck M, Patwary N, Haunschild G, Guzvic M, Reimelt C, Grauvogl M, Eichner N, Weber F, Hartkopf AD, Taran F-A, Brucker SY, Fehm T, Rack B, Buchholz S, Spang R, Meister G, Aguirre-Ghiso JA, Klein CA. 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SKB was (is) a consultant for QIAGEN. Currently, OH is receiving consulting fees from Riemser, Roche, Amgen, Pfizer, Elsai, Hexal, MSD, Novartis and Daiichi Sankyo and RK from Tesaro, Astra-Zeneca and Medtronic, respectively.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Written informed consent was obtained from all patients and the study was approved by the institutional review board (05\/2856 & 16-6915-BO).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}