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