Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma.

Journal: Nature communications
PMID: 38092727

Abstract

Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.

Authors

  • Julien Calderaro
    Department of Pathology, Henri Mondor University Hospital, Créteil, France.
  • Narmin Ghaffari Laleh
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Qinghe Zeng
    Centre d'Histologie, d'Imagerie et de Cytométrie (CHIC), Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.
  • Pascale Maillé
    INSERM U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", Créteil, France.
  • Loetitia Favre
    Université Paris Est Créteil, INSERM, IMRB, F-94010, Créteil, France.
  • Anaïs Pujals
    Université Paris Est Créteil, INSERM, IMRB, F-94010, Créteil, France.
  • Christophe Klein
    Centre d'Histologie, d'Imagerie et de Cytométrie (CHIC), Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.
  • Céline Bazille
    Caen University Hospital, Department of Pathology, Caen, France.
  • Lara R Heij
    Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.
  • Arnaud Uguen
    CHRU Brest, Department of Pathology, Brest, 29220, France.
  • Tom Luedde
    Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Aachen, Germany.
  • Luca Di Tommaso
    Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • Aurélie Beaufrère
    Assistance Publique-Hôpitaux de Paris, Beaujon University Hospital, Department of Pathology, F-92110, Clichy, France.
  • Augustin Chatain
    Inserm, U955, Team 18, Créteil, France.
  • Delphine Gastineau
    Inserm, U955, Team 18, Créteil, France.
  • Cong Trung Nguyen
    Department of Pathology, E Hospital, Hanoi Medical University, Hanoi, Vietnam.
  • Hiep Nguyen-Canh
    Pathology Center, Bachmai Hospital, Hanoi, Vietnam.
  • Khuyen Nguyen Thi
    Pathology and Molecular biology Center, National Cancer Hospital, Hanoi, Vietnam.
  • Viviane Gnemmi
    University Lille, UMR9020-U1277, Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France.
  • Rondell P Graham
    Mayo Clinic, Rochester, MN, USA.
  • Frédéric Charlotte
    Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Pathology, Paris, France.
  • Dominique Wendum
    Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, Department of Pathology, Paris, France.
  • Mukul Vij
    Institute of GI Sciences and Liver Transplantation Gleneagles Global Health City Chennai India.
  • Daniela S Allende
    Department of Hepatobiliary Pathology, Cleveland Clinic Foundation, Cleveland, OH, USA.
  • Federico Aucejo
    Department of Surgery, Cleveland Clinic, Cleveland, OH, USA.
  • Alba Diaz
    Barcelona Clinic Liver Cancer (BCLC) Group, Department of Pathology, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
  • Benjamin Rivière
    Department of Pathology, Gui-de-Chauliac University Hospital, 80, avenue Augustin-Fliche, 34295, Montpellier, France.
  • Astrid Herrero
    Department of Liver SurgerySt-Eloi University HospitalMontpellierFrance.
  • Katja Evert
    Institute of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
  • Diego Francesco Calvisi
    Institute of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
  • Jérémy Augustin
    Département de pathologie, hôpital universitaire Henri-Mondor, assistance publique-hôpitaux de Paris, Créteil, France; Inserm U955 Team 18, université Paris-Est-Créteil, faculté de Médecine, Créteil, France. Electronic address: jeremy.augustin@aphp.fr.
  • Wei Qiang Leow
    Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore.
  • Howard Ho Wai Leung
    Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Emmanuel Boleslawski
    CHU Lille, Department of Digestive and Hepatobiliary Surgery, Lille, France.
  • Mohamed Rela
    Institute of GI Sciences and Liver Transplantation Gleneagles Global Health City Chennai India.
  • Arnaud François
    Rouen University Hospital, Department of Pathology, Rouen, France.
  • Anthony Wing-Hung Cha
    Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • Alejandro Forner
    Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, ICMDM, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
  • Maria Reig
    Barcelona Clinic Liver Cancer (BCLC), Liver Unit, Hospital Clinic of Barcelona, IDIBAPS, CIBEREHD, Universidad de Barcelona, Barcelona, Spain.
  • Manon Allaire
    Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Hepatology, Paris, France.
  • Olivier Scatton
    Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Digestive and Hepatobiliary Surgery, Paris, France.
  • Denis Chatelain
    Centre Hospitalier Universitaire d'Amiens, Département de Pathologie, Amiens, France.
  • Camille Boulagnon-Rombi
    Laboratoire d'anatomie et cytologie pathologique, CHU Reims, 51100 Reims, France.
  • Nathalie Sturm
    Department of Pathology, University Hospital, Grenoble, France.
  • Benjamin Menahem
    Caen University Hospital, Department of Digestive and Hepatobiliary Surgery, Caen, France.
  • Eric Frouin
    Poitiers University Hospital, Department of Pathology, Poitiers, France.
  • David Tougeron
    Poitiers University Hospital, Department of Hepatogastroenterology and Oncology, Poitiers, France.
  • Christophe Tournigand
    Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Medical Oncology, Créteil, France.
  • Emmanuelle Kempf
    Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Medical Oncology, Créteil, France.
  • Haeryoung Kim
    Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
  • Massih Ningarhari
    CHU Lille, Department of Hepatology, Lille, France.
  • Sophie Michalak-Provost
    Angers University Hospital, Department of Pathology, Angers, France.
  • Purva Gopal
    Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.
  • Raffaele Brustia
    Assistance Publique-Hôpitaux de Paris, Henri Mondor University Hospital, Department of Digestive and Hepatobiliary Surgery, Créteil, France.
  • Eric Vibert
    Department of Liver Surgery and Transplantation, AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; Inserm Unité 1193, Villejuif, France. Electronic address: eric.vibert@pbr.aphp.fr.
  • Kornelius Schulze
    Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Darius F Rüther
    Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Sören A Weidemann
    Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Rami Rhaiem
    Reims University Hospital, Department of Digestive and Hepatobiliary Surgery, Reims, France.
  • Jean-Michel Pawlotsky
    Paris Est Créteil University, UPEC, Créteil, France.
  • Xuchen Zhang
    Department of Pathology, Yale School of Medicine, 310 Cedar Street, New Haven, CT, 06520, USA.
  • Alain Luciani
    Medical Imaging Department, Henri Mondor University Hospital, AP-HP, Créteil, France, Inserm, U955, Team 18, 94000 Créteil, France.
  • Sébastien Mulé
    Medical Imaging Department, Henri Mondor University Hospital, AP-HP, Créteil, France, Inserm, U955, Team 18, 94000 Créteil, France.
  • Alexis Laurent
    Assistance Publique-Hôpitaux de Paris, Department of Hepatobiliary and Digestive Surgery, Henri Mondor Hospital, Créteil, France.
  • Giuliana Amaddeo
    Paris Est Créteil University, UPEC, Créteil, France.
  • Hélène Regnault
    Assistance Publique-Hôpitaux de Paris, Department of Hepatology, Henri Mondor Hospital, Créteil, France.
  • Eleonora De Martin
    Assistance Publique-Hôpitaux de Paris, Paul Brousse University Hospital, Department of Hepatology, Paris, France.
  • Christine Sempoux
    Institute of Pathology, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.
  • Pooja Navale
    Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, 63110, USA.
  • Maria Westerhoff
    Department of Pathology University of Michigan, Ann Arbor, MI, USA.
  • Regina Cheuk-Lam Lo
    Department of Pathology, The University of Hong Kong, Pok Fu Lam, Hong Kong, China.
  • Jan Bednarsch
    Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
  • Annette Gouw
    Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands.
  • Catherine Guettier
    Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
  • Marie Lequoy
    Assistance Publique-Hôpitaux de Paris, Saint Antoine University Hospital, Department of Hepatology, Paris, France.
  • Kenichi Harada
    Department of Urology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
  • Pimsiri Sripongpun
    Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand.
  • Poowadon Wetwittayaklang
    Prince of Songkla University, Department of Pathology, Hat Yai, Thailand.
  • Nicolas Lomenie
    Laboratoire d'Informatique Paris Descartes (LIPADE), Université de Paris, Paris, France.
  • Jarukit Tantipisit
    Prince of Songkla University, Department of Pathology, Hat Yai, Thailand.
  • Apichat Kaewdech
    Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand.
  • Jeanne Shen
    Center for Artificial Intelligence in Medicine and Imaging, Stanford University, 1701 Page Mill Road, Palo Alto, CA, 94304, USA. jeannes@stanford.edu.
  • Valerie Paradis
    Université Paris Cité, Dpt of Pathology - FHU MOSAIC, Beaujon Hospital, INSERM U1149, Clichy, France.
  • Stefano Caruso
    Université Paris Est Créteil, INSERM, IMRB, F-94010, Créteil, France.
  • Jakob Nikolas Kather
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.

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