TY - JOUR
T1 - An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®
AU - Varga, Zsuzsanna
AU - Lebeau, Annette
AU - Bu, Hong
AU - Hartmann, Arndt
AU - Penault-Llorca, Frederique
AU - Guerini-Rocco, Elena
AU - Schraml, Peter
AU - Symmans, Fraser
AU - Stoehr, Robert
AU - Teng, Xiaodong
AU - Turzynski, Andreas
AU - von Wasielewski, Reinhard
AU - Gürtler, Claudia
AU - Laible, Mark
AU - Schlombs, Kornelia
AU - Joensuu, Heikki
AU - Keller, Thomas
AU - Sinn, Peter
AU - Sahin, Ugur
AU - Bartlett, John
AU - Viale, Giuseppe
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/5/11
Y1 - 2017/5/11
N2 - 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.
AB - 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.
KW - Breast cancer
KW - ERBB2
KW - ESR1
KW - FFPE
KW - MKI67
KW - MammaTyper
KW - PGR
KW - RT-qPCR
KW - Reproducibility
UR - http://www.scopus.com/inward/record.url?scp=85019101718&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019101718&partnerID=8YFLogxK
U2 - 10.1186/s13058-017-0848-z
DO - 10.1186/s13058-017-0848-z
M3 - Article
C2 - 28490348
AN - SCOPUS:85019101718
SN - 1465-5411
VL - 19
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 55
ER -