Abstract

Histopathological images contain morphological markers of disease progression that have diagnostic and predictive values. In this study, we demonstrate how deep learning framework can be used for an automatic classification of Renal Cell Carcinoma (RCC) subtypes, and for identification of features that predict survival outcome from digital histopathological images. Convolutional neural networks (CNN’s) trained on whole-slide images distinguish clear cell and chromophobe RCC from normal tissue with a classification accuracy of 93.39% and 87.34%, respectively. Further, a CNN trained to distinguish clear cell, chromophobe and papillary RCC achieves a classification accuracy of 94.07%. Here, we introduced a novel support vector machine-based method that helped to break the multi-class classification task into multiple binary classification tasks which not only improved the performance of the model but also helped to deal with data imbalance. Finally, we extracted the morphological features from high probability tumor regions identified by the CNN to predict patient survival outcome of most common clear cell RCC. The generated risk index based on both tumor shape and nuclei features are significantly associated with patient survival outcome. These results highlight that deep learning can play a role in both cancer diagnosis and prognosis.

Highlights

  • Kidney Cancer accounts for nearly 3.8% of adult cancers and is among the 10 most common cancers in both men and women

  • KIRC is characterized with loss of chromosome 3p and mutation of the von Hippel–Lindau (VHL) gene while KIRP is characterized by trisomy of chromosomes and loss of chromosome 9p6,7

  • We obtained 93.39% and 87.34% (Tables 1 and 2) patch-wise accuracy on the test set for KIRC and KICH, respectively

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Summary

Introduction

Kidney Cancer accounts for nearly 3.8% of adult cancers and is among the 10 most common cancers in both men and women. KIRC patients have an overall 5-year survival rate of 55–60%9–11 whereas for KIRP patients, it varies from 80–90%12,13 and for KICH patients, it is 90%14 Due to these distinct biological and clinical behavior of subtypes, accurate detection of RCC and its subtypes is vital for the clinical management of patients. The Cancer Genome Atlas (TCGA)[21,22] project has resulted in the creation of large repositories of digital H & E whole-slide images (WSI) of RCC. These images are acquired at 20x and 40x magnifications with size varying from 10000–100000 pixels, which are visually tricky to analyze and interpret accurately. CNN’s have been successful in capturing the complex tissue patterns and have been widely used in biomedical imaging for segmentation as well as for classification tasks in cancers such as breast[30,31,32], lung[33,34,35,36] and prostate[37]

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