An Advanced Deep Learning Approach for Ki-67 Stained Hotspot Detection and Proliferation Rate Scoring for Prognostic Evaluation of Breast Cancer

摘要

Being a non-histone protein, Ki-67 is one of the essential biomarkers for the immunohistochemical assessment of proliferation rate in breast cancer screening and grading. The Ki-67 signature is always sensitive to radiotherapy and chemotherapy. Due to random morphological, color and intensity variations of cell nuclei (immunopositive and immunonegative), manual/subjective assessment of Ki-67 scoring is error-prone and time-consuming. Hence, several machine learning approaches have been reported; nevertheless, none of them had worked on deep learning based hotspots detection and proliferation scoring. In this article, we suggest an advanced deep learning model for computerized recognition of candidate hotspots and subsequent proliferation rate scoring by quantifying Ki-67 appearance in breast cancer immunohistochemical images. Unlike existing Ki-67 scoring techniques, our methodology uses Gamma mixture model (GMM) with Expectation-Maximization for seed point detection and patch selection and deep learning, comprises with decision layer, for hotspots detection and proliferation scoring. Experimental results provide 93% precision, 0.88% recall and 0.91% F-score value. The model performance has also been compared with the pathologists’ manual annotations and recently published articles. In future, the proposed deep learning framework will be highly reliable and beneficial to the junior and senior pathologists for fast and efficient Ki-67 scoring.