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Clinical Validation of


CRC and GC (n=282) formalin-Fixed Paraffin-Embedded (FFPE) tissue from patients treated with irinotecan were immunostained and the percent of positive nuclei was quantitatively and statistically analyzed as shown in Figures 2 and 3. The sensitivity, specificity, positive and negative predictive value of P-topoI-Dx is similar or better than the FDA-approved IHC-based predictive biomarker used in clinical oncology (Table).

Figure. 2. Quantitative analysis of P-topoI-Dx IHC assays. Colorectal cancer FFPE slides were immunostained with anti-topoI-pS10 and scanned by Aperio AT2 scanner. The images were quantitatively analyzed by image scope software package using the V9 algorithm. A. Representative image of P-topoI-Dx negative immunostaining. B. Quantitative analysis of the selected area from A demonstrated 0+ staining (blue nuclei). C. Quantitation of the selected area from B. D. Representative image of TopoI-pS10 positive nuclear staining in a separate patient. E. Quantitative analysis of the annotated area in Figure D and numbers are displayed in Figure F. 

Figure.3. Prediction of Resistance and Probability of Positive Response. Probability of Positive Response as Function of Percentage of Positive Nuclei, as Determined by Logistic Regression showing GC training (red line), GC validation (black dashed line) and CRC validation (blue dotted line).

Table  SEQ Table \* ARABIC 1. Comparative Predictive values of IHC. *PDL-1 IHC test was FDA approved for immuno oncology based on higher response rate in patients with more than 50% total proportion score (TPS). **HER2 IHC test (HercepTest) was FDA approved twenty years ago based on 64% predictive value. However, a change in the scoring system resulted in much higher PPV/NPV of this test.

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