eprintid: 22945 rev_number: 12 eprint_status: archive userid: 1589 dir: disk0/00/02/29/45 datestamp: 2017-05-15 09:01:29 lastmod: 2024-05-07 15:16:07 status_changed: 2017-05-15 09:01:29 type: article metadata_visibility: show creators_name: Varga, Zsuzsanna creators_name: Lebeau, Annette creators_name: Bu, Hong creators_name: Hartmann, Arndt creators_name: Penault-Llorca, Frederique creators_name: Guerini-Rocco, Elena creators_name: Schraml, Peter creators_name: Symmans, Fraser creators_name: Stoehr, Robert creators_name: Teng, Xiaodong creators_name: Turzynski, Andreas creators_name: von Wasielewski, Reinhard creators_name: Gürtler, Claudia creators_name: Laible, Mark creators_name: Schlombs, Kornelia creators_name: Joensuu, Heikki creators_name: Keller, Thomas creators_name: Sinn, Hans-Peter creators_name: Sahin, Ugur creators_name: Bartlett, John creators_name: Viale, Giuseppe title: An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper® subjects: ddc-610 divisions: i-912000 abstract: Background: Accurate determination of the predictive markers human epidermal growth factor receptor 2 (HER2/ERBB2), estrogen receptor (ER/ESR1), progesterone receptor (PgR/PGR), and marker of proliferation Ki67 (MKI67) is indispensable for therapeutic decision making in early breast cancer. In this multicenter prospective study, we addressed the issue of inter- and intrasite reproducibility using the recently developed reverse transcription-quantitative real-time polymerase chain reaction-based MammaTyper® test. Methods: Ten international pathology institutions participated in this study and determined messenger RNA expression levels of ERBB2, ESR1, PGR, and MKI67 in both centrally and locally extracted RNA from formalin-fixed, paraffin-embedded breast cancer specimens with the MammaTyper® test. Samples were measured repeatedly on different days within the local laboratories, and reproducibility was assessed by means of variance component analysis, Fleiss’ kappa statistics, and interclass correlation coefficients (ICCs). Results: Total variations in measurements of centrally and locally prepared RNA extracts were comparable; therefore, statistical analyses were performed on the complete dataset. Intersite reproducibility showed total SDs between 0.21 and 0.44 for the quantitative single-marker assessments, resulting in ICC values of 0.980–0.998, demonstrating excellent agreement of quantitative measurements. Also, the reproducibility of binary single-marker results (positive/negative), as well as the molecular subtype agreement, was almost perfect with kappa values ranging from 0.90 to 1.00. Conclusions: On the basis of these data, the MammaTyper® has the potential to substantially improve the current standards of breast cancer diagnostics by providing a highly precise and reproducible quantitative assessment of the established breast cancer biomarkers and molecular subtypes in a decentralized workup. date: 2017 publisher: BioMed Central id_scheme: DOI ppn_swb: 1659085764 own_urn: urn:nbn:de:bsz:16-heidok-229459 language: eng bibsort: VARGAZSUZSANINTERNAT2017 full_text_status: public publication: Breast Cancer Research volume: 19 number: 55 place_of_pub: London pagerange: 1-13 issn: 1465-542X citation: Varga, Zsuzsanna ; Lebeau, Annette ; Bu, Hong ; Hartmann, Arndt ; Penault-Llorca, Frederique ; Guerini-Rocco, Elena ; Schraml, Peter ; Symmans, Fraser ; Stoehr, Robert ; Teng, Xiaodong ; Turzynski, Andreas ; von Wasielewski, Reinhard ; Gürtler, Claudia ; Laible, Mark ; Schlombs, Kornelia ; Joensuu, Heikki ; Keller, Thomas ; Sinn, Hans-Peter ; Sahin, Ugur ; Bartlett, John ; Viale, Giuseppe (2017) An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®. Breast Cancer Research, 19 (55). pp. 1-13. ISSN 1465-542X document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/22945/1/13058_2017_Article_848.pdf