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


Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
12 2022
Historique:
received: 28 12 2021
revised: 08 07 2022
accepted: 18 07 2022
pubmed: 21 8 2022
medline: 23 11 2022
entrez: 20 8 2022
Statut: ppublish

Résumé

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. 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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 35987274
pii: S0168-8278(22)02983-X
doi: 10.1016/j.jhep.2022.07.019
pii:
doi:

Substances chimiques

Nestin 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1586-1597

Informations de copyright

Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest JC consults for Crosscope, KB is Crosscope Chief Technology Officer, JS is Crosscope Chief Executive Officer. Please refer to the accompanying ICMJE disclosure forms for further details.

Auteurs

Julien Calderaro (J)

Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France; European Reference Network (ERN) RARE-LIVER. Electronic address: julien.calderaro@aphp.fr.

Luca Di Tommaso (L)

Department of Pathology, Humanitas University, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy.

Pascale Maillé (P)

Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France.

Aurélie Beaufrère (A)

Assistance Publique-Hôpitaux de Paris, Beaujon University Hospital, Department of Pathology, F-92110 Clichy, France; Université de Paris, Inflammation Research Center, Inserm, U1149, CNRS, ERL8252, F-75018 Paris, France.

Cong Trung Nguyen (CT)

Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France.

Lara Heij (L)

Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany; Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.

Viviane Gnemmi (V)

University Lille, UMR9020-U1277, Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France; CHU Lille, Institute of Pathology, Lille, France.

Rondell P Graham (RP)

Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Rochester, MN, USA.

Frédéric Charlotte (F)

Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Pathology, Paris, France.

Suzanne Chartier (S)

Assistance Publique-Hôpitaux de Paris, Saint Antoine University Hospital, Department of Pathology, Paris, France; INSERM UMR_S 938, Centre de Recherche Saint Antoine (CRSA), Faculté de Médecine Sorbonne Université, 75012, Paris, France.

Dominique Wendum (D)

Assistance Publique-Hôpitaux de Paris, Saint Antoine University Hospital, Department of Pathology, Paris, France; INSERM UMR_S 938, Centre de Recherche Saint Antoine (CRSA), Faculté de Médecine Sorbonne Université, 75012, Paris, France.

Mukul Vij (M)

Department of Pathology, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India.

Daniela Allende (D)

Department of Gastrointestinal and Hepatobiliary Pathology, Cleveland Clinic Foundation, Cleveland, OH, USA.

Alba Diaz (A)

Barcelona Clinic Liver Cancer (BCLC) Group, Department of Pathology, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.

Carla Fuster (C)

Barcelona Clinic Liver Cancer (BCLC) Group, Department of Pathology, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.

Benjamin Rivière (B)

Department of Pathology, Gui-de-Chauliac University Hospital, 80, avenue Augustin-Fliche, 34295 Montpellier, France.

Astrid Herrero (A)

Department of Digestive and Hepatobiliary Surgery, Gui-de-Chauliac University Hospital, 80, avenue Augustin-Fliche, 34295 Montpellier, France.

Jérémy Augustin (J)

Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France.

Katja Evert (K)

Institute of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.

Diego Francesco Calvisi (DF)

Institute of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.

Wei Qiang Leow (WQ)

Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore.

Howard Ho Wai Leung (HHW)

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.

Jan Bednarsch (J)

Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.

Emmanuel Boleslawski (E)

CHU Lille, Department of Digestive and Hepatobiliary Surgery, Lille, France.

Mohamed Rela (M)

Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India.

Anthony Wing-Hung Chan (AW)

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.

Alejandro Forner (A)

European Reference Network (ERN) RARE-LIVER; Barcelona Clinic Liver Cancer (BCLC), Liver Unit, Hospital Clinic of Barcelona, IDIBAPS, CIBEREHD, Universidad de Barcelona, Barcelona, Spain.

Maria Reig (M)

European Reference Network (ERN) RARE-LIVER; Barcelona Clinic Liver Cancer (BCLC), Liver Unit, Hospital Clinic of Barcelona, IDIBAPS, CIBEREHD, Universidad de Barcelona, Barcelona, Spain.

Anaïs Pujals (A)

Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France.

Loetitia Favre (L)

Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France.

Manon Allaire (M)

Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Hepatology, Paris, France.

Olivier Scatton (O)

Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Digestive and Hepatobiliary Surgery, Paris, France.

Arnaud Uguen (A)

CHRU Brest, Department of Pathology, Brest 29220 France; Univ Brest, Inserm, CHU de Brest, LBAI, UMR1227, Brest, France.

Eric Trépo (E)

Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.

Lukas Otero Sanchez (LO)

Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.

Denis Chatelain (D)

Amiens University Hospital, Department of Pathology, Amiens, France.

Myriam Remmelink (M)

Erasme University Hospital, Department of Pathology, Brussels, Belgium.

Camille Boulagnon-Rombi (C)

Reims University Hospital, Department of Pathology, Reims, France.

Céline Bazille (C)

Caen University Hospital, Department of Pathology, Caen, France.

Nathalie Sturm (N)

Department of Pathology, University Hospital, Grenoble, France; Translational Innovation in Medicine and Complexity, Centre National de la Recherche Scientifique UMR5525, La Tronche, France.

Benjamin Menahem (B)

Caen University Hospital, Department of Digestive and Hepatobiliary Surgery, Caen, France.

Eric Frouin (E)

Poitiers University Hospital, Department of Pathology, Poitiers, France.

David Tougeron (D)

Poitiers University Hospital, Department of Hepatogastroenterology and Oncology, Poitiers, France.

Christophe Tournigand (C)

Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Medical Oncology, Créteil, France.

Emmanuelle Kempf (E)

Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Medical Oncology, Créteil, France.

Haeryoung Kim (H)

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Massih Ningarhari (M)

CHU Lille, Department of Hepatology, Lille, France.

Sophie Michalak-Provost (S)

Angers University Hospital, Department of Pathology, Angers, France.

Jakob Nikolas Kather (JN)

Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany; Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.

Annette S H Gouw (ASH)

Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands.

Purva Gopal (P)

Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.

Raffaele Brustia (R)

Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Inserm, U955, Team 18, Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor University Hospital, Department of Digestive and Hepatobiliary Surgery, Paris, France.

Eric Vibert (E)

Assistance Publique-Hôpitaux de Paris, Paul Brousse University Hospital, Department of Digestive and Hepatobiliary Surgery, Paris, France.

Kornelius Schulze (K)

Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Darius F Rüther (DF)

Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Sören A Weidemann (SA)

Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Rami Rhaiem (R)

Reims University Hospital, Department of Digestive and Hepatobiliary Surgery, Reims, France.

Jean-Charles Nault (JC)

Liver Unit, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, Bobigny, France; University Paris 13, Paris, France; Cordeliers Research Center, Sorbonne University, INSERM UMR 1138 Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France.

Alexis Laurent (A)

Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor University Hospital, Department of Digestive and Hepatobiliary Surgery, Paris, France.

Giuliana Amaddeo (G)

Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Inserm, U955, Team 18, Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Hepatology, Créteil, France.

Hélène Regnault (H)

Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Hepatology, Créteil, France.

Eleonora de Martin (E)

Assistance Publique-Hôpitaux de Paris, Paul Brousse University Hospital, Department of Hepatology, Paris, France.

Christine Sempoux (C)

Institute of Pathology, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.

Pooja Navale (P)

Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, 63110, USA.

Jayendra Shinde (J)

Crosscope, Mountain View, CA, USA; Crosscope, Mountain View, Pune, India.

Ketan Bacchuwar (K)

Crosscope, Mountain View, CA, USA; Crosscope, Mountain View, Pune, India.

Maria Westerhoff (M)

Department of Pathology, University of Michigan, Ann Arbor MI, USA.

Regina Cheuk-Lam Lo (RC)

Department of Pathology, The University of Hong Kong, Pok Fu Lam, Hong Kong; State Key Laboratory of Liver Research, (The University of Hong Kong), Pok Fu Lam, Hong Kong.

Mylène Sebbagh (M)

Assistance Publique-Hôpitaux de Paris, Paul Brousse University Hospital, Department of Pathology, Villejuif, France.

Catherine Guettier (C)

Assistance Publique-Hôpitaux de Paris, Paul Brousse University Hospital, Department of Pathology, Villejuif, France.

Marie Lequoy (M)

Assistance Publique-Hôpitaux de Paris, Saint Antoine University Hospital, Department of Hepatology, Paris, France.

Mina Komuta (M)

Department of Pathology, International University of Health and Welfare, School of Medicine, Chiba 286-8520, Japan; Department of Pathology, School of Medicine, Keio University, Tokyo 160-8582, Japan; Department of Pathology, School of Medicine, Kurume University, Fukuoka 830-0011, Japan.

Marianne Ziol (M)

Assistance Publique-Hôpitaux de Paris, Department of Pathology, Jean Verdier Hospital, Bondy, France; Functional Genomics of Solid Tumors, INSERM-1162, Paris 13 University, Paris, France.

Valérie Paradis (V)

Assistance Publique-Hôpitaux de Paris, Beaujon University Hospital, Department of Pathology, F-92110 Clichy, France; Université de Paris, Inflammation Research Center, Inserm, U1149, CNRS, ERL8252, F-75018 Paris, France.

Jeanne Shen (J)

Center for Artificial Intelligence in Medicine and Imaging, Stanford University, 1701 Page Mill Road, Palo Alto, CA, 94304, USA;; Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.

Stefano Caruso (S)

Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France.

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