机构：[1]Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.[2]Private Group Practice for Pathology and PathoPlan GbR, Lübeck, Germany.[3]Department of Pathology and Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.四川大学华西医院[4]Institute of Pathology, University Erlangen-Nürnberg, Erlangen, Germany.[5]Centre Jean Perrin, Centre regional de Lutte contre le cancer d’Auvergne, Clermont-Ferrand, France.[6]European Institute of Oncology, University of Milan, Milan, Italy.[7]University of Texas MD Anderson Cancer Center, Houston, TX, USA.[8]Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.浙江大学医学院附属第一医院[9]Institute of Pathology, Klinikum Region Hannover, Hannover, Germany.[10]BioNTech Diagnostics GmbH, Mainz, Germany.[11]Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.[12]ACOMED Statistik, Leipzig, Germany.[13]Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany.[14]Transformative Pathology, Ontario Institute for Cancer Research (OICR), Toronto, ON, Canada.
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 (R) 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 (R) 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 (R) 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.
基金：
The study was sponsored by BioNTech Diagnostics GmbH. Employees of
BioNTech Diagnostics GmbH were involved in study design and management.
第一作者机构：[1]Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
通讯作者：
推荐引用方式(GB/T 7714)：
Zsuzsanna Varga,Annette Lebeau,Hong Bu,et al.An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper (R)[J].BREAST CANCER RESEARCH.2017,19(1):55.doi:10.1186/s13058-017-0848-z.
APA：
Zsuzsanna Varga,Annette Lebeau,Hong Bu,Arndt Hartmann,Frederique Penault-Llorca...&Giuseppe Viale.(2017).An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper (R).BREAST CANCER RESEARCH,19,(1)
MLA：
Zsuzsanna Varga,et al."An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper (R)".BREAST CANCER RESEARCH 19..1(2017):55
