Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Julien Calderaro - , Université Paris-Est Créteil, Hôpital Henri Mondor, European Reference Network (ERN) RARE-LIVER (Author)
  • Luca Di Tommaso - , Humanitas University (Author)
  • Pascale Maillé - , Université Paris-Est Créteil, Hôpital Henri Mondor (Author)
  • Aurélie Beaufrère - , Hopital Beaujon, Centre de Recherche sur l'Inflammation (Author)
  • Cong Trung Nguyen - , Université Paris-Est Créteil, Hôpital Henri Mondor (Author)
  • Lara Heij - , RWTH Aachen University (Author)
  • Viviane Gnemmi - , Université de Lille, University Hospital of Lille (Author)
  • Rondell P. Graham - , Mayo Clinic Rochester, MN (Author)
  • Frédéric Charlotte - , Sorbonne Université (Author)
  • Suzanne Chartier - , Sorbonne Université (Author)
  • Dominique Wendum - , Sorbonne Université (Author)
  • Mukul Vij - , Bharath Institute of Higher Education and Research (Author)
  • Daniela Allende - , Cleveland Clinic Foundation (Author)
  • Alba Diaz - , University of Barcelona (Author)
  • Carla Fuster - , University of Barcelona (Author)
  • Benjamin Rivière - , CHU Montpellier (Author)
  • Astrid Herrero - , CHU Montpellier (Author)
  • Jérémy Augustin - , Université Paris-Est Créteil, Hôpital Henri Mondor (Author)
  • Katja Evert - , University of Regensburg (Author)
  • Diego Francesco Calvisi - , University of Regensburg (Author)
  • Wei Qiang Leow - , Singapore General Hospital (Author)
  • Howard Ho Wai Leung - , Chinese University of Hong Kong (Author)
  • Jan Bednarsch - , RWTH Aachen University (Author)
  • Emmanuel Boleslawski - , University Hospital of Lille (Author)
  • Mohamed Rela - , Bharath Institute of Higher Education and Research (Author)
  • Anthony Wing Hung Chan - , Chinese University of Hong Kong (Author)
  • Alejandro Forner - , European Reference Network (ERN) RARE-LIVER, University of Barcelona (Author)
  • Maria Reig - , European Reference Network (ERN) RARE-LIVER, University of Barcelona (Author)
  • Anaïs Pujals - , Université Paris-Est Créteil, Hôpital Henri Mondor (Author)
  • Loetitia Favre - , Université Paris-Est Créteil, Hôpital Henri Mondor (Author)
  • Manon Allaire - , Sorbonne Université (Author)
  • Olivier Scatton - , Sorbonne Université (Author)
  • Arnaud Uguen - , CHU de Brest, Université de Bretagne Occidentale (Author)
  • Eric Trépo - , Université libre de Bruxelles (ULB) (Author)
  • Lukas Otero Sanchez - , Université libre de Bruxelles (ULB) (Author)
  • Denis Chatelain - , Université de Picardie Jules Verne (Author)
  • Myriam Remmelink - , Université libre de Bruxelles (ULB) (Author)
  • Camille Boulagnon-Rombi - , CHU de Reims (Author)
  • Céline Bazille - , Université de Caen (Author)
  • Nathalie Sturm - , CHU de Grenoble, French National Centre for Scientific Research (CNRS) (Author)
  • Benjamin Menahem - , Université de Caen (Author)
  • Eric Frouin - , CHU de Poitiers (Author)
  • David Tougeron - , CHU de Poitiers (Author)
  • Christophe Tournigand - , Hôpital Henri Mondor (Author)
  • Emmanuelle Kempf - , Hôpital Henri Mondor (Author)
  • Haeryoung Kim - , Seoul National University (Author)
  • Massih Ningarhari - , University Hospital of Lille (Author)
  • Sophie Michalak-Provost - , Université d'Angers (Author)
  • Jakob Nikolas Kather - , RWTH Aachen University, Heidelberg University  (Author)
  • Annette S.H. Gouw - , University of Groningen (Author)

Abstract

Background & Aims: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs. Methods: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCCs) and 221 intrahepatic cholangiocarcinomas (iCCAs). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver-operating characteristic curves and Cox regression modeling. Results: Nestin was able to distinguish cHCC-CCA from HCC with AUCs of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from iCCA (AUCs of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA (“Nestin High”, >30% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies. Conclusion: We show in different clinical settings that Nestin has diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy. Lay summary: There are different types of primary liver cancers (i.e. cancers that originate in the liver). Accurately identifying a specific subtype of primary liver cancer (and determining its associated prognosis) is important as it can have a major impact on treatment allocation. Herein, we show that a protein called Nestin could be used to refine risk stratification and improve treatment allocation for patients with combined hepatocellular carcinoma, a rare but highly aggressive subtype of primary liver cancer.

Details

Original languageEnglish
Pages (from-to)1586-1597
Number of pages12
JournalJournal of hepatology
Volume77
Issue number6
Publication statusPublished - Dec 2022
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 35987274

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • cancer, cholangiocarcinoma, combined hepatocellular-cholangiocarcinoma, hepatocellular carcinoma, liver, nestin

Library keywords