Automated segmentation of cell membranes to evaluate HER2 status in whole slide images using a modified deep learning network

Khameneh F. D., Razavi S., Kamasak M. E.

COMPUTERS IN BIOLOGY AND MEDICINE, vol.110, pp.164-174, 2019 (SCI-Expanded) identifier identifier identifier


The uncontrollable growth of cells in the breast tissue causes breast cancer which is the second most common type of cancer affecting women in the United States. Normally, human epidermal growth factor receptor 2 (HER2) proteins are responsible for the division and growth of healthy breast cells. HER2 status is currently assessed using immunohistochemistry (IHC) as well as in situ hybridization (ISH) in equivocal cases. Manual HER2 evaluation of IHC stained microscopic images involves an error-prone, tedious, inter-observer variable, and time-consuming routine lab work due to diverse staining, overlapped regions, and non-homogeneous remarkable large slides. To address these issues, digital pathology offers reproducible, automatic, and objective analysis and interpretation of whole slide image (WSI). In this paper, we present a machine learning (ML) framework to segment, classify, and quantify IHC breast cancer images in an effective way. The proposed method consists of two major classifying and segmentation parts. Since HER2 is associated with tumors of an epithelial region and most of the breast tumors originate in epithelial tissue, it is crucial to develop an approach to segment different tissue structures. The proposed technique is comprised of three steps. In the first step, a superpixel-based support vector machine (SVM) feature learning classifier is proposed to classify epithelial and stromal regions from WSI. In the second stage, on classified epithelial regions, a convolutional neural network (CNN) based segmentation method is applied to segment membrane regions. Finally, divided tiles are merged and the overall score of each slide is evaluated. Experimental results for 127 slides are presented and compared with state-of-the-art handcraft and deep learning-based approaches. The experiments demonstrate that the proposed method achieved promising performance on IHC stained data. The presented automated algorithm was shown to outperform other approaches in terms of superpixel based classifying of epithelial regions and segmentation of membrane staining using CNN.