TY - JOUR
T1 - Decentral gene expression analysis for ER+/Her2-breast cancer
T2 - Results of a proficiency testing program for the EndoPredict assay
AU - Denkert, Carsten
AU - Kronenwett, Ralf
AU - Schlake, Werner
AU - Bohmann, Kerstin
AU - Penzel, Roland
AU - Weber, Karsten E.
AU - Höfler, Heinz
AU - Lehmann, Ulrich
AU - Schirmacher, Peter
AU - Specht, Katja
AU - Rudas, Margaretha
AU - Kreipe, Hans Heinrich
AU - Schraml, Peter
AU - Schlake, Gudrun
AU - Bago-Horvath, Zsuzsanna
AU - Tiecke, Frank
AU - Varga, Zsuzsanna
AU - Moch, Holger
AU - Schmidt, Marcus
AU - Prinzler, Judith
AU - Kerjaschki, Dontscho
AU - Sinn, Bruno Valentin
AU - Müller, Berit Maria
AU - Filipits, Martin
AU - Petry, Christoph
AU - Dietel, Manfred
N1 - Funding Information:
Acknowledgments We would like to thank Manuela Averdick, Britta Beyer, Nicole Bleuel, Angelika Bönisch, Angelika Brüntgens, Susanne Dettwiler, Franziska Haufe, Tina Holper, Ines Koch, Tanja Ropers, Claudia Roth, Elisa Schipper, Petra Wachs, Claudia Windbergs for their excellent technical assistance and Martina Eickmann for her editorial assistance. Part of this work was funded by the German Ministry of Science and Technology (BMBF) in the NEOpredict project (Project number 01ES0725).
PY - 2012/3
Y1 - 2012/3
N2 - Gene expression profiles provide important information about the biology of breast tumors and can be used to develop prognostic tests. However, the implementation of quantitative RNA-based testing in routine molecular pathology has not been accomplished, so far. The EndoPredict assay has recently been described as a quantitative RT-PCRbased multigene expression test to identify a subgroup of hormone-receptor-positive tumors that have an excellent prognosis with endocrine therapy only. To transfer this test from bench to bedside, it is essential to evaluate the test- performance in a multicenter setting in different molecular pathology laboratories. In this study, we have evaluated the EndoPredict (EP) assay in seven different molecular pathology laboratories in Germany, Austria, and Switzerland. A set of ten formalin-fixed paraffin-embedded tumors was tested in the different labs, and the variance and accuracy of the EndoPredict assays were determined using predefined reference values. Extraction of a sufficient amount of RNA and generation of a valid EP score was possible for all 70 study samples (100%). The EP scores measured by the individual participants showed an excellent correlation with the reference values, respectively, as reflected by Pearson correlation coefficients ranging from 0.987 to 0.999. The Pearson correlation coefficient of all values compared to the reference value was 0.994. All laboratories determined EP scores for all samples differing not more than 1.0 score units from the pre-defined references. All samples were assigned to the correct EP risk group, resulting in a sensitivity and specificity of 100%, a concordance of 100%, and a kappa of 1.0. Taken together, the EndoPredict test could be successfully implemented in all seven participating laboratories and is feasible for reliable decentralized assessment of gene expression in luminal breast cancer.
AB - Gene expression profiles provide important information about the biology of breast tumors and can be used to develop prognostic tests. However, the implementation of quantitative RNA-based testing in routine molecular pathology has not been accomplished, so far. The EndoPredict assay has recently been described as a quantitative RT-PCRbased multigene expression test to identify a subgroup of hormone-receptor-positive tumors that have an excellent prognosis with endocrine therapy only. To transfer this test from bench to bedside, it is essential to evaluate the test- performance in a multicenter setting in different molecular pathology laboratories. In this study, we have evaluated the EndoPredict (EP) assay in seven different molecular pathology laboratories in Germany, Austria, and Switzerland. A set of ten formalin-fixed paraffin-embedded tumors was tested in the different labs, and the variance and accuracy of the EndoPredict assays were determined using predefined reference values. Extraction of a sufficient amount of RNA and generation of a valid EP score was possible for all 70 study samples (100%). The EP scores measured by the individual participants showed an excellent correlation with the reference values, respectively, as reflected by Pearson correlation coefficients ranging from 0.987 to 0.999. The Pearson correlation coefficient of all values compared to the reference value was 0.994. All laboratories determined EP scores for all samples differing not more than 1.0 score units from the pre-defined references. All samples were assigned to the correct EP risk group, resulting in a sensitivity and specificity of 100%, a concordance of 100%, and a kappa of 1.0. Taken together, the EndoPredict test could be successfully implemented in all seven participating laboratories and is feasible for reliable decentralized assessment of gene expression in luminal breast cancer.
KW - Breast cancer
KW - Control Prognosis
KW - Quality
KW - mRNA
UR - http://www.scopus.com/inward/record.url?scp=84860320539&partnerID=8YFLogxK
U2 - 10.1007/s00428-012-1204-4
DO - 10.1007/s00428-012-1204-4
M3 - Article
C2 - 22371223
AN - SCOPUS:84860320539
SN - 0945-6317
VL - 460
SP - 251
EP - 259
JO - Virchows Archiv
JF - Virchows Archiv
IS - 3
ER -
