Deep learning detects genetic alterations in cancer histology generated by adversarial networks.

Journal: The Journal of pathology
Published Date:

Abstract

Deep learning can detect microsatellite instability (MSI) from routine histology images in colorectal cancer (CRC). However, ethical and legal barriers impede sharing of images and genetic data, hampering development of new algorithms for detection of MSI and other biomarkers. We hypothesized that histology images synthesized by conditional generative adversarial networks (CGANs) retain information about genetic alterations. To test this, we developed a 'histology CGAN' which was trained on 256 patients (training cohort 1) and 1457 patients (training cohort 2). The CGAN synthesized 10 000 synthetic MSI and non-MSI images which contained a range of tissue types and were deemed realistic by trained observers in a blinded study. Subsequently, we trained a deep learning detector of MSI on real or synthetic images and evaluated the performance of MSI detection in a held-out set of 142 patients. When trained on real images from training cohort 1, this system achieved an area under the receiver operating curve (AUROC) of 0.742 [0.681, 0.854]. Training on the larger cohort 2 only marginally improved the AUROC to 0.757 [0.707, 0.869]. Training on purely synthetic data resulted in an AUROC of 0.743 [0.658, 0.801]. Training on both real and synthetic data further increased AUROC to 0.777 [0.715, 0.821]. We conclude that synthetic histology images retain information reflecting underlying genetic alterations in colorectal cancer. Using synthetic instead of real images to train deep learning systems yields non-inferior classifiers. This approach can be used to create large shareable data sets or to augment small data sets with rare molecular features. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Authors

  • Jeremias Krause
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Heike I Grabsch
    Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands.
  • Matthias Kloor
    Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
  • Michael Jendrusch
    Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
  • Amelie Echle
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Roman David Buelow
    Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.
  • Peter Boor
    Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
  • Tom Luedde
    Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Aachen, Germany.
  • Titus J Brinker
    National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Christian Trautwein
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Alexander T Pearson
    Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Philip Quirke
    Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom.
  • Josien Jenniskens
    Department of Epidemiology, Maastricht University Medical Center+, Maastricht, The Netherlands.
  • Kelly Offermans
    Department of Epidemiology, Maastricht University Medical Center+, Maastricht, The Netherlands.
  • Piet A van den Brandt
    Department of Epidemiology, Maastricht University Medical Center+, Maastricht, The Netherlands.
  • Jakob Nikolas Kather
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.