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Quantitative Analysis of Diagnostic Guidelines for HER2-Status Assessment  Albrecht Stenzinger, Moritz von Winterfeld, Sebastian Aulmann, Arne Warth, Wilko.

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Presentation on theme: "Quantitative Analysis of Diagnostic Guidelines for HER2-Status Assessment  Albrecht Stenzinger, Moritz von Winterfeld, Sebastian Aulmann, Arne Warth, Wilko."— Presentation transcript:

1 Quantitative Analysis of Diagnostic Guidelines for HER2-Status Assessment 
Albrecht Stenzinger, Moritz von Winterfeld, Sebastian Aulmann, Arne Warth, Wilko Weichert, Carsten Denkert, Josef Rüschoff, Manfred Dietel, Frederick Klauschen  The Journal of Molecular Diagnostics  Volume 14, Issue 3, Pages (May 2012) DOI: /j.jmoldx Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

2 Figure 1 A: Estimated probability distributions from eight representative HER2 SISH cases (1 to 8, used for simulations in Figure 2; same color codes). B: Exemplary case (breast cancer) stained with dual-color SISH for HER2 (black) and chromosome 17 (red). The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx ) Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

3 Figure 2 Analysis of simulated case data. A: Variability of HER2/CHR17 ratios as a function of the number of evaluated cells and signal distribution (compare Figure 1A, matched color codes of distribution and graph). B: Differences between maximum and minimum HER2/CHR17 ratios computed in 1000 MCSs as a function of cell number and distribution. C: Estimate of the percentage of diagnosed HER2/CHR17 ratios that differ by at least 0.2 based on 1000 simulations for different numbers of evaluated cells and different distributions. D: Percentage of diagnosed HER2/CHR17 ratios that differ by at least 0.1, 0.2, 0.3, 0.5, 0.7, and 1.0 for different numbers of evaluated cells averaged over all eight distributions, based on 1000 MCSs. The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx ) Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

4 Figure 3 A: Difference between ratios of separate-slide SISH and single-slide double-color ISH (heat map, blue = 0 to dark red/brown = 1.5). Separate slide SISH constantly underestimates amplification ratios compared with double-color ISH with individual cell ratio calculation (MCS results, SD = 2). Each heat map element represents the difference between the two ratio calculation approaches for a simulated case, in which the x axis value denotes the mean HER2 ISH count and the y axis value the mean chromosome 17 count. B: HER2 amplified (blue) and not amplified (green) independent of used method. Red indicates borderline cases diagnosed as not amplified using the separate ISH method and amplified using double-color ISH (MCS results, same data as in Figure 1). The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx ) Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions


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