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An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®

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...

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Autores principales: 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, Peter, Sahin, Ugur, Bartlett, John, Viale, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426065/
https://www.ncbi.nlm.nih.gov/pubmed/28490348
http://dx.doi.org/10.1186/s13058-017-0848-z
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author 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, Peter
Sahin, Ugur
Bartlett, John
Viale, Giuseppe
author_facet 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, Peter
Sahin, Ugur
Bartlett, John
Viale, Giuseppe
author_sort Varga, Zsuzsanna
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-017-0848-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-54260652017-05-12 An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper® 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, Peter Sahin, Ugur Bartlett, John Viale, Giuseppe Breast Cancer Res Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-017-0848-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-11 2017 /pmc/articles/PMC5426065/ /pubmed/28490348 http://dx.doi.org/10.1186/s13058-017-0848-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
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, Peter
Sahin, Ugur
Bartlett, John
Viale, Giuseppe
An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®
title An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®
title_full An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®
title_fullStr An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®
title_full_unstemmed An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®
title_short An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®
title_sort international reproducibility study validating quantitative determination of erbb2, esr1, pgr, and mki67 mrna in breast cancer using mammatyper®
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426065/
https://www.ncbi.nlm.nih.gov/pubmed/28490348
http://dx.doi.org/10.1186/s13058-017-0848-z
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