Automated detection of vascular remodeling in tumor-draining lymph nodes by the deep-learning tool HEV-finder.

Journal: The Journal of pathology
Published Date:

Abstract

Vascular remodeling is common in human cancer and has potential as future biomarkers for prediction of disease progression and tumor immunity status. It can also affect metastatic sites, including the tumor-draining lymph nodes (TDLNs). Dilation of the high endothelial venules (HEVs) within TDLNs has been observed in several types of cancer. We recently demonstrated that it is a premetastatic effect that can be linked to tumor invasiveness in breast cancer. Manual visual assessment of changes in vascular morphology is a tedious and difficult task, limiting high-throughput analysis. Here we present a fully automated approach for detection and classification of HEV dilation. By using 12,524 manually classified HEVs, we trained a deep-learning model and created a graphical user interface for visualization of the results. The tool, named the HEV-finder, selectively analyses HEV dilation in specific regions of the lymph nodes. We evaluated the HEV-finder's ability to detect and classify HEV dilation in different types of breast cancer compared to manual annotations. Our results constitute a successful example of large-scale, fully automated, and user-independent, image-based quantitative assessment of vascular remodeling in human pathology and lay the ground for future exploration of HEV dilation in TDLNs as a biomarker. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Authors

  • Tove Bekkhus
    The Beijer Laboratory, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
  • Christophe Avenel
    Department of Information Technology, Uppsala University, Uppsala, Sweden.
  • Sabella Hanna
    The Beijer Laboratory, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
  • Mathias Franzén Boger
    The Beijer Laboratory, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
  • Anna Klemm
    Department of Information Technology, Uppsala University, Uppsala, Sweden.
  • Daniel Vasiliu Bacovia
    The Beijer Laboratory, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
  • Fredrik Wärnberg
    Department of Surgery at Institute of Clinical Sciences, Sahlgrenska University Hospital Göteborg, Göteborg, Sweden.
  • Carolina Wählby
    1 Centre for Image Analysis/SciLifeLab, Uppsala University, Uppsala, Sweden.
  • Maria H Ulvmar
    The Beijer Laboratory, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.