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

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Varga , Z , Lebeau , A , Bu , H , Hartmann , A , Penault-Llorca , F , Guerini-Rocco , E , Schraml , P , Symmans , F , Stoehr , R , Teng , X , Turzynski , A , von Wasielewski , R , Guertler , C , Laible , M , Schlombs , K , Joensuu , H , Keller , T , Sinn , P , Sahin , U , Bartlett , J & Viale , G 2017 , ' An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper (R) ' , Breast Cancer Research , vol. 19 , 55 . https://doi.org/10.1186/s13058-017-0848-z

Title: An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper (R)
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; Guertler, Claudia; Laible, Mark; Schlombs, Kornelia; Joensuu, Heikki; Keller, Thomas; Sinn, Peter; Sahin, Ugur; Bartlett, John; Viale, Giuseppe
Contributor: University of Helsinki, Clinicum
Date: 2017-05-11
Language: eng
Number of pages: 13
Belongs to series: Breast Cancer Research
ISSN: 1465-542X
URI: http://hdl.handle.net/10138/190726
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 (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.
Subject: MammaTyper
Reproducibility
RT-qPCR
FFPE
Breast cancer
ERBB2
ESR1
PGR
MKI67
RECURRENCE SCORE
AMERICAN-SOCIETY
RECEPTOR EXPRESSION
DISTANT RECURRENCE
ESTROGEN-RECEPTOR
ENDOCRINE THERAPY
WORKING GROUP
RT-QPCR
KI67
RECOMMENDATIONS
3122 Cancers
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