DeepSDCS: Dissecting cancer proliferation heterogeneity in Ki67 digital whole slide images

Priya Lakshmi Narayanan, Andrew Dodson, Barry Gusterson, Mitchell Dowsett, Yinyin Yuan

Abstract: Ki67 is an important biomarker for breast cancer. Classification of positive and negative Ki67 cells in histology slides is a common approach to determine cancer proliferation status. However, there is a lack of generalizable and accurate methods to automate Ki67 scoring in large-scale patient cohorts. In this work, we have employed a novel deep learning technique based on hypercolumn descriptors for cell classification in Ki67 images. Specifically, we developed the Simultaneous Detection and Cell Segmentation (DeepSDCS) network to perform cell segmentation and detection. VGG16 network was used for the training and fine tuning to training data. We extracted the hypercolumn descriptors of each cell to form the vector of activation from specific layers to capture features at different granularity. Features from these layers that correspond to the same pixel were propagated using a stochastic gradient descent optimizer to yield the detection of the nuclei and the final cell segmentations. Subsequently, seeds generated from cell segmentation were propagated to a spatially constrained convolutional neural network for the classification of the cells into stromal, lymphocyte, Ki67-positive cancer cell, and Ki67-negative cancer cell. Cells were subsequently classified using a spatially constrained network. We validated its accuracy in the context of a large-scale clinical trial of oestrogen-receptor-positive breast cancer. We achieved 99.06% and 89.59% accuracy on two separate test sets of Ki67 stained breast cancer dataset comprising biopsy and whole-slide images.

Author Affiliation: Centre for Evolution and Cancer, Institute of Cancer Research, London, United Kingdom, Centre for Molecular Pathology, Royal Marsden Hospital, London, United Kingdom, Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London, United Kingdom, Academic Department of Biochemistry, Royal Marsden Hospital, London, UK

Keywords: Ki67 cell classification, Simultaneous detection and cell segmentation.