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

Zsuzsanna Varga, Annette Lebeau, Hong Bu, Arndt Hartmann, Frederique Penault-Llorca, Elena Guerini-Rocco, Peter Schraml, Fraser Symmans, Robert Stoehr, Xiaodong Teng, Andreas Turzynski, Reinhard von Wasielewski, Claudia Gürtler, Mark Laible, Kornelia Schlombs, Heikki Joensuu, Thomas Keller, Peter Sinn, Ugur Sahin, John BartlettGiuseppe Viale

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number55
JournalBreast Cancer Research
Volume19
Issue number1
DOIs
Publication statusPublished - May 11 2017

Keywords

  • Breast cancer
  • ERBB2
  • ESR1
  • FFPE
  • MammaTyper
  • MKI67
  • PGR
  • Reproducibility
  • RT-qPCR

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®'. Together they form a unique fingerprint.

  • Cite this

    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., Gürtler, C., Laible, M., Schlombs, K., Joensuu, H., Keller, T., Sinn, P., Sahin, U., ... Viale, G. (2017). An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®. Breast Cancer Research, 19(1), [55]. https://doi.org/10.1186/s13058-017-0848-z