{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:01:31Z","timestamp":1791450091535,"version":"4.3.3"},"reference-count":36,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017037","name":"Cepheid","doi-asserted-by":"publisher","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}],"id":[{"id":"10.13039\/100017037","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Estrogen receptor (ER), progesterone receptor (PgR), Ki-67, and HER2 immunohistochemistry (IHC) together with HER2 in situ hybridization (ISH) are utilized to classify invasive breast cancer (IBC) into predictive molecular subtypes. As IHC evaluation may be hampered by analytical errors, gene expression assays could offer a reliable alternative. In this first Europe-wide external quality assessment (EQA) study, we investigated performance of mRNA-based Xpert\u00ae Breast Cancer STRAT4 (CE-IVD) in five European laboratories. The cohort comprised ten pre-therapy IBC core biopsies diagnosed in the coordinating center (CC). STRAT4 binary (positive or negative) mRNA results of each marker (ESR1, PGR, ERBB2,\u00a0MKI67) were compared with the gold standard IHC\/ISH performed by the CC. Sensitivity, specificity, and accuracy of ESR1 and ERBB2 mRNA were 100% for all samples. In contrast, PGR expression was falsely negative for one case by two sites and MKI67 falsely negative for two cases (respectively by four and one sites). These cases had STRAT4 expression values close to assay cut-offs and immunohistochemically presented heterogeneous low positive PgR and heterogeneous Ki-67. Our EQA shows that STRAT4 mRNA assay may be a reproducible method to evaluate ER, PgR, HER2, and Ki-67 status. However, cases with expression values close to assay cut-offs should be carefully reviewed.<\/jats:p>","DOI":"10.3390\/cancers13184718","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:04:23Z","timestamp":1632211463000},"page":"4718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Reproducibility of mRNA-Based Testing of ESR1, PGR, ERBB2, and MKI67 Expression in Invasive Breast Cancer\u2014A Europe-Wide External Quality Assessment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0315-1229","authenticated-orcid":false,"given":"Ramona","family":"Erber","sequence":"first","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4885-8471","authenticated-orcid":false,"given":"Peter Andreas","family":"Fasching","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Ruebner","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"St\u00f6hr","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias Wilhelm","family":"Beckmann","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Zentgraf","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Popp","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi","family":"Weidler","sequence":"additional","affiliation":[{"name":"Cepheid, Department of Medical and Scientific Affairs and Strategy, Oncology, 904 Caribbean Drive, Sunnyvale, CA 94089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Simon","sequence":"additional","affiliation":[{"name":"Cepheid, Department of Medical and Scientific Affairs and Strategy, Oncology, 904 Caribbean Drive, Sunnyvale, CA 94089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffi","family":"Becker","sequence":"additional","affiliation":[{"name":"Cepheid, Department of Medical and Scientific Affairs and Strategy, Oncology, 904 Caribbean Drive, Sunnyvale, CA 94089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6889-1493","authenticated-orcid":false,"given":"Hanna","family":"Huebner","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Fischer","sequence":"additional","affiliation":[{"name":"Qualit\u00e4tssicherungs-Initiative Pathologie QuIP GmbH, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Guerini Rocco","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, IEO, European Institute of Oncology, IRCCS, 20141 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Viale","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, IEO, European Institute of Oncology, IRCCS, 20141 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Cayre","sequence":"additional","affiliation":[{"name":"Centre Jean Perrin, Department of Pathology and Clermont Auvergne University, INSERM, U1240, \u201cImagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques\u201d, F-63011 Clermont Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederique","family":"Penault-Llorca","sequence":"additional","affiliation":[{"name":"Centre Jean Perrin, Department of Pathology and Clermont Auvergne University, INSERM, U1240, \u201cImagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques\u201d, F-63011 Clermont Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Caniego Casas","sequence":"additional","affiliation":[{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria, 28034 Madrid, Spain"},{"name":"CIBER-ONC, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"P\u00e9rez-Mi\u00e9s","sequence":"additional","affiliation":[{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria, 28034 Madrid, Spain"},{"name":"CIBER-ONC, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Pathology, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"},{"name":"Facultad de Medicina, Universidad de Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6730-5066","authenticated-orcid":false,"given":"Jos\u00e9","family":"Palacios","sequence":"additional","affiliation":[{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria, 28034 Madrid, Spain"},{"name":"CIBER-ONC, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Pathology, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"},{"name":"Facultad de Medicina, Universidad de Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-0476","authenticated-orcid":false,"given":"Paul","family":"Jank","sequence":"additional","affiliation":[{"name":"Institute of Pathology, UKGM\u2014University Hospital Marburg, Philipps-University Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Denkert","sequence":"additional","affiliation":[{"name":"Institute of Pathology, UKGM\u2014University Hospital Marburg, Philipps-University Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Khoury","sequence":"additional","affiliation":[{"name":"MVZ Helios Hospital Emil von Behring GmbH, 14165 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mairinger","sequence":"additional","affiliation":[{"name":"MVZ Helios Hospital Emil von Behring GmbH, 14165 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4011-4638","authenticated-orcid":false,"given":"Fulvia","family":"Ferrazzi","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"},{"name":"Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/35021093","article-title":"Molecular portraits of human breast tumours","volume":"406","author":"Perou","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10869","DOI":"10.1073\/pnas.191367098","article-title":"Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications","volume":"98","author":"Sorlie","year":"2001","journal-title":"Proc. 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