Title:Increasing the usefulness of already existing annotations through WSI registration

Abstract:Computational pathology methods have the potential to improve access to precision medicine, as well as the reproducibility and accuracy of pathological diagnoses. Particularly the analysis of whole-slide-images (WSIs) of immunohistochemically (IHC) stained tissue sections could benefit from computational pathology methods. However, scoring biomarkers such as KI67 in IHC WSIs often necessitates the detection of areas of invasive cancer. Training cancer detection models often requires annotations, which is time-consuming and therefore costly. Currently, cancer regions are typically annotated in WSIs of haematoxylin and eosin (H&E) stained tissue sections. In this study, we investigate the possibility to register annotations that were made in H&E WSIs to their IHC counterparts. Two pathologists annotated regions of invasive cancer in WSIs of 272 breast cancer cases. For each case, a matched H&E and KI67 WSI are available, resulting in 544 WSIs with invasive cancer annotations. We find that cancer detection CNNs that were trained with annotations registered from the H&E to the KI67 WSIs only differ slightly in calibration but not in performance compared to cancer detection models trained on annotations made directly in the KI67 WSIs in a test set consisting of 54 cases. The mean slide-level AUROC is 0.974 [0.964, 0.982] for models trained with the KI67 annotations and 0.974 [0.965, 0.982] for models trained using registered annotations. This indicates that WSI registration has the potential to reduce the need for IHC-specific annotations. This could significantly increase the usefulness of already existing annotations.