An End-to-End Deep Learning Histochemical Scoring System for Breast Cancer TMA.

One of the methods for stratifying different molecular classes of breast cancer is the Nottingham prognostic index plus, which uses breast cancer relevant biomarkers to stain tumor tissues prepared on tissue microarray (TMA). To determine the molecular class of the tumor, pathologists will have to manually mark the nuclei activity biomarkers through a microscope and use a semi-quantitative assessment method to assign a histochemical score (H-Score) to each TMA core. Manually marking positively stained nuclei is a time-consuming, imprecise, and subjective process, which will lead to inter-observer and intra-observer discrepancies. In this paper, we present an end-to-end deep learning system, which directly predicts the H-Score automatically. Our system imitates the pathologists' decision process and uses one fully convolutional network (FCN) to extract all nuclei region (tumor and non-tumor), a second FCN to extract tumor nuclei region, and a multi-column convolutional neural network, which takes the outputs of the first two FCNs and the stain intensity description image as an input and acts as the high-level decision making mechanism to directly output the H-Score of the input TMA image. To the best of our knowledge, this is the first end-to-end system that takes a TMA image as the input and directly outputs a clinical score. We will present experimental results, which demonstrate that the H-Scores predicted by our model have very high and statistically significant correlation with experienced pathologists' scores and that the H-Score discrepancy between our algorithm and the pathologists is on par with the inter-subject discrepancy between the pathologists.