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Decentral gene expression analysis for ER+/Her2- breast cancer: results of a proficiency testing program for the EndoPredict assay.

Denkert C, Kronenwett R, Schlake W, Bohmann K, Penzel R, Weber KE, Höfler H, Lehmann U, Schirmacher P, Specht K, Rudas M, Kreipe HH, Schraml P, Schlake G, Bago-Horvath Z, Tiecke F, Varga Z, Moch H, Schmidt M, Prinzler J, Kerjaschki D, Sinn BV, Müller BM, Filipits M, Petry C, Dietel M - Virchows Arch. (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, Charité Hospital, Campus Mitte, Schumannstr. 20/21, 10117 Berlin, Germany. carsten.denkert@charite.de

ABSTRACT
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-PCR-based 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.

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Results of the decentral measurement of 70 tumor samples from ten different tumors. The central reference value is marked in red, the blue labels represent the seven different measurements at the seven institutes of pathology
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Fig2: Results of the decentral measurement of 70 tumor samples from ten different tumors. The central reference value is marked in red, the blue labels represent the seven different measurements at the seven institutes of pathology

Mentions: Therefore, the EP scores of 69 of the 70 measurements were correct with respect to the reference value and one was just at the pre-specified cutoff. For the EP score, the results of the individual measurements are shown in Fig. 2. As shown in Fig. 3, there was a high concordance in the analysis of the different genes in the seven laboratories. The EndoPredict score is arranged as a linear combination of eight genes for increased robustness. Three genes (BIRC5, DHCR7, UBE2C) are positively associated with the EP score, the other genes (AZGP1, IL6ST, MGP, RBBP8, STC2) yield to a smaller score the higher they are expressed. For details on the biological interpretation of the genes, see supplementary appendix in Filipits et al. [14].Fig. 2


Decentral gene expression analysis for ER+/Her2- breast cancer: results of a proficiency testing program for the EndoPredict assay.

Denkert C, Kronenwett R, Schlake W, Bohmann K, Penzel R, Weber KE, Höfler H, Lehmann U, Schirmacher P, Specht K, Rudas M, Kreipe HH, Schraml P, Schlake G, Bago-Horvath Z, Tiecke F, Varga Z, Moch H, Schmidt M, Prinzler J, Kerjaschki D, Sinn BV, Müller BM, Filipits M, Petry C, Dietel M - Virchows Arch. (2012)

Results of the decentral measurement of 70 tumor samples from ten different tumors. The central reference value is marked in red, the blue labels represent the seven different measurements at the seven institutes of pathology
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3306560&req=5

Fig2: Results of the decentral measurement of 70 tumor samples from ten different tumors. The central reference value is marked in red, the blue labels represent the seven different measurements at the seven institutes of pathology
Mentions: Therefore, the EP scores of 69 of the 70 measurements were correct with respect to the reference value and one was just at the pre-specified cutoff. For the EP score, the results of the individual measurements are shown in Fig. 2. As shown in Fig. 3, there was a high concordance in the analysis of the different genes in the seven laboratories. The EndoPredict score is arranged as a linear combination of eight genes for increased robustness. Three genes (BIRC5, DHCR7, UBE2C) are positively associated with the EP score, the other genes (AZGP1, IL6ST, MGP, RBBP8, STC2) yield to a smaller score the higher they are expressed. For details on the biological interpretation of the genes, see supplementary appendix in Filipits et al. [14].Fig. 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, Charité Hospital, Campus Mitte, Schumannstr. 20/21, 10117 Berlin, Germany. carsten.denkert@charite.de

ABSTRACT
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-PCR-based 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.

Show MeSH
Related in: MedlinePlus