Development and Validation of Fully Automatic Deep Learning-Based Algorithms for Immunohistochemistry Reporting of Invasive Breast Ductal Carcinoma

Abstract

Immunohistochemistry (IHC) analysis is a well-accepted and widely used method for molecular subtyping, a procedure for prognosis and targeted therapy of breast carcinoma, the most common type of tumor affecting women. There are four molecular biomarkers namely progesterone receptor (PR), estrogen receptor (ER), antigen Ki67, and human epidermal growth factor receptor 2 (HER2) whose assessment is needed under IHC procedure to decide prognosis as well as predictors of response to therapy. However, IHC scoring is based on subjective microscopic examination of tumor morphology and suffers from poor reproducibility, high subjectivity, and often incorrect scoring in low-score cases. In this paper, we present, a deep learning-based semi-supervised trained, fully automatic, decision support system (DSS) for IHC scoring of invasive ductal carcinoma. Our system automatically detects the tumor region removing artifacts and scores based on Allred standard. The system is developed using 3 million pathologist-annotated image patches from 300 slides, fifty thousand in-house cell annotations, and forty thousand pixels marking of HER2 membrane. We have conducted multicentric trials at four centers with three different types of digital scanners in terms of percentage agreement with doctors. And achieved agreements of 95, 92, 88 and 82 percent for Ki67, HER2, ER, and PR stain categories, respectively. In addition to overall accuracy, we found that there is 5 percent of cases where pathologist have changed their score in favor of algorithm score while reviewing with detailed algorithmic analysis. Our approach could improve the accuracy of IHC scoring and subsequent therapy decisions, particularly where specialist expertise is unavailable. Our system is highly modular. The proposed algorithm modules can be used to develop DSS for other cancer types.