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

Julien Calderaro; Luca Di Tommaso; Pascale Maillé; Aurélie Beaufrère; Cong Trung Nguyen; Lara Heij; Viviane Gnemmi; Rondell P. Graham; Frédéric Charlotte; Suzanne Chartier; Dominique Wendum; Mukul Vij; Daniela Allende; Alba Diaz; Carla Fuster; Benjamin Rivière; Astrid Herrero; Jérémy Augustin; Katja Evert; Diego Francesco Calvisi; Wei Qiang Leow; Howard Ho Wai Leung; Jan Bednarsch; Emmanuel Boleslawski; Mohamed Rela; Anthony Wing Hung Chan; Alejandro Forner; Maria Reig; Anaïs Pujals; Loetitia Favre; Manon Allaire; Olivier Scatton; Arnaud Uguen; Eric Trépo; Lukas Otero Sanchez; Denis Chatelain; Myriam Remmelink; Camille Boulagnon-Rombi; Céline Bazille; Nathalie Sturm; Benjamin Menahem; Eric Frouin; David Tougeron; Christophe Tournigand; Emmanuelle Kempf; Haeryoung Kim; Massih Ningarhari; Sophie Michalak-Provost; Jakob Nikolas Kather; Annette S.H. Gouw; Purva Gopal; Raffaele Brustia; Eric Vibert; Kornelius Schulze; Darius F. Rüther; Sören A. Weidemann; Rami Rhaiem; Jean Charles Nault; Alexis Laurent; Giuliana Amaddeo; Hélène Regnault; Eleonora de Martin; Christine Sempoux; Pooja Navale; Jayendra Shinde; Ketan Bacchuwar; Maria Westerhoff; Regina Cheuk Lam Lo; Mylène Sebbagh; Catherine Guettier; Marie Lequoy; Mina Komuta; Marianne Ziol; Valérie Paradis; Jeanne Shen; Stefano Caruso

doi:10.1016/j.jhep.2022.07.019

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

Julien Calderaro, Luca Di Tommaso, Pascale Maillé, Aurélie Beaufrère, Cong Trung Nguyen, Lara Heij, Viviane Gnemmi, Rondell P. Graham, Frédéric Charlotte, Suzanne Chartier, Dominique Wendum, Mukul Vij, Daniela Allende, Alba Diaz, Carla Fuster, Benjamin Rivière, Astrid Herrero, Jérémy Augustin, Katja Evert, Diego Francesco CalvisiWei Qiang Leow, Howard Ho Wai Leung, Jan Bednarsch, Emmanuel Boleslawski, Mohamed Rela, Anthony Wing Hung Chan, Alejandro Forner, Maria Reig, Anaïs Pujals, Loetitia Favre, Manon Allaire, Olivier Scatton, Arnaud Uguen, Eric Trépo, Lukas Otero Sanchez, Denis Chatelain, Myriam Remmelink, Camille Boulagnon-Rombi, Céline Bazille, Nathalie Sturm, Benjamin Menahem, Eric Frouin, David Tougeron, Christophe Tournigand, Emmanuelle Kempf, Haeryoung Kim, Massih Ningarhari, Sophie Michalak-Provost, Jakob Nikolas Kather, Annette S.H. Gouw, Purva Gopal, Raffaele Brustia, Eric Vibert, Kornelius Schulze, Darius F. Rüther, Sören A. Weidemann, Rami Rhaiem, Jean Charles Nault, Alexis Laurent, Giuliana Amaddeo, Hélène Regnault, Eleonora de Martin, Christine Sempoux, Pooja Navale, Jayendra Shinde, Ketan Bacchuwar, Maria Westerhoff, Regina Cheuk Lam Lo, Mylène Sebbagh, Catherine Guettier, Marie Lequoy, Mina Komuta, Marianne Ziol, Valérie Paradis, Jeanne Shen, Stefano Caruso

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1586-1597
Number of pages	12
Journal	Journal of Hepatology
Volume	77
Issue number	6
DOIs	https://doi.org/10.1016/j.jhep.2022.07.019
State	Published - Dec 2022

Keywords

cancer
cholangiocarcinoma
combined hepatocellular-cholangiocarcinoma
hepatocellular carcinoma
liver
nestin

ASJC Scopus subject areas

Hepatology

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10.1016/j.jhep.2022.07.019

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Calderaro, J., Di Tommaso, L., Maillé, P., Beaufrère, A., Nguyen, C. T., Heij, L., Gnemmi, V., Graham, R. P., Charlotte, F., Chartier, S., Wendum, D., Vij, M., Allende, D., Diaz, A., Fuster, C., Rivière, B., Herrero, A., Augustin, J., Evert, K., ... Caruso, S. (2022). Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma. Journal of Hepatology, 77(6), 1586-1597. https://doi.org/10.1016/j.jhep.2022.07.019

Calderaro, J, Di Tommaso, L, Maillé, P, Beaufrère, A, Nguyen, CT, Heij, L, Gnemmi, V, Graham, RP, Charlotte, F, Chartier, S, Wendum, D, Vij, M, Allende, D, Diaz, A, Fuster, C, Rivière, B, Herrero, A, Augustin, J, Evert, K, Calvisi, DF, Leow, WQ, Leung, HHW, Bednarsch, J, Boleslawski, E, Rela, M, Chan, AWH, Forner, A, Reig, M, Pujals, A, Favre, L, Allaire, M, Scatton, O, Uguen, A, Trépo, E, Sanchez, LO, Chatelain, D, Remmelink, M, Boulagnon-Rombi, C, Bazille, C, Sturm, N, Menahem, B, Frouin, E, Tougeron, D, Tournigand, C, Kempf, E, Kim, H, Ningarhari, M, Michalak-Provost, S, Kather, JN, Gouw, ASH, Gopal, P, Brustia, R, Vibert, E, Schulze, K, Rüther, DF, Weidemann, SA, Rhaiem, R, Nault, JC, Laurent, A, Amaddeo, G, Regnault, H, de Martin, E, Sempoux, C, Navale, P, Shinde, J, Bacchuwar, K, Westerhoff, M, Lo, RCL, Sebbagh, M, Guettier, C, Lequoy, M, Komuta, M, Ziol, M, Paradis, V, Shen, J & Caruso, S 2022, 'Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma', Journal of Hepatology, vol. 77, no. 6, pp. 1586-1597. https://doi.org/10.1016/j.jhep.2022.07.019

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title = "Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma",

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.",

keywords = "cancer, cholangiocarcinoma, combined hepatocellular-cholangiocarcinoma, hepatocellular carcinoma, liver, nestin",

author = "Julien Calderaro and {Di Tommaso}, Luca and Pascale Maill{\'e} and Aur{\'e}lie Beaufr{\`e}re and Nguyen, {Cong Trung} and Lara Heij and Viviane Gnemmi and Graham, {Rondell P.} and Fr{\'e}d{\'e}ric Charlotte and Suzanne Chartier and Dominique Wendum and Mukul Vij and Daniela Allende and Alba Diaz and Carla Fuster and Benjamin Rivi{\`e}re and Astrid Herrero and J{\'e}r{\'e}my Augustin and Katja Evert and Calvisi, {Diego Francesco} and Leow, {Wei Qiang} and Leung, {Howard Ho Wai} and Jan Bednarsch and Emmanuel Boleslawski and Mohamed Rela and Chan, {Anthony Wing Hung} and Alejandro Forner and Maria Reig and Ana{\"i}s Pujals and Loetitia Favre and Manon Allaire and Olivier Scatton and Arnaud Uguen and Eric Tr{\'e}po and Sanchez, {Lukas Otero} and Denis Chatelain and Myriam Remmelink and Camille Boulagnon-Rombi and C{\'e}line Bazille and Nathalie Sturm and Benjamin Menahem and Eric Frouin and David Tougeron and Christophe Tournigand and Emmanuelle Kempf and Haeryoung Kim and Massih Ningarhari and Sophie Michalak-Provost and Kather, {Jakob Nikolas} and Gouw, {Annette S.H.} and Purva Gopal and Raffaele Brustia and Eric Vibert and Kornelius Schulze and R{\"u}ther, {Darius F.} and Weidemann, {S{\"o}ren A.} and Rami Rhaiem and Nault, {Jean Charles} and Alexis Laurent and Giuliana Amaddeo and H{\'e}l{\`e}ne Regnault and {de Martin}, Eleonora and Christine Sempoux and Pooja Navale and Jayendra Shinde and Ketan Bacchuwar and Maria Westerhoff and Lo, {Regina Cheuk Lam} and Myl{\`e}ne Sebbagh and Catherine Guettier and Marie Lequoy and Mina Komuta and Marianne Ziol and Val{\'e}rie Paradis and Jeanne Shen and Stefano Caruso",

note = "Publisher Copyright: {\textcopyright} 2022 European Association for the Study of the Liver",

year = "2022",

month = dec,

doi = "10.1016/j.jhep.2022.07.019",

language = "English (US)",

volume = "77",

pages = "1586--1597",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "Elsevier",

number = "6",

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TY - JOUR

T1 - Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma

AU - Calderaro, Julien

AU - Di Tommaso, Luca

AU - Maillé, Pascale

AU - Beaufrère, Aurélie

AU - Nguyen, Cong Trung

AU - Heij, Lara

AU - Gnemmi, Viviane

AU - Graham, Rondell P.

AU - Charlotte, Frédéric

AU - Chartier, Suzanne

AU - Wendum, Dominique

AU - Vij, Mukul

AU - Allende, Daniela

AU - Diaz, Alba

AU - Fuster, Carla

AU - Rivière, Benjamin

AU - Herrero, Astrid

AU - Augustin, Jérémy

AU - Evert, Katja

AU - Calvisi, Diego Francesco

AU - Leow, Wei Qiang

AU - Leung, Howard Ho Wai

AU - Bednarsch, Jan

AU - Boleslawski, Emmanuel

AU - Rela, Mohamed

AU - Chan, Anthony Wing Hung

AU - Forner, Alejandro

AU - Reig, Maria

AU - Pujals, Anaïs

AU - Favre, Loetitia

AU - Allaire, Manon

AU - Scatton, Olivier

AU - Uguen, Arnaud

AU - Trépo, Eric

AU - Sanchez, Lukas Otero

AU - Chatelain, Denis

AU - Remmelink, Myriam

AU - Boulagnon-Rombi, Camille

AU - Bazille, Céline

AU - Sturm, Nathalie

AU - Menahem, Benjamin

AU - Frouin, Eric

AU - Tougeron, David

AU - Tournigand, Christophe

AU - Kempf, Emmanuelle

AU - Kim, Haeryoung

AU - Ningarhari, Massih

AU - Michalak-Provost, Sophie

AU - Kather, Jakob Nikolas

AU - Gouw, Annette S.H.

AU - Gopal, Purva

AU - Brustia, Raffaele

AU - Vibert, Eric

AU - Schulze, Kornelius

AU - Rüther, Darius F.

AU - Weidemann, Sören A.

AU - Rhaiem, Rami

AU - Nault, Jean Charles

AU - Laurent, Alexis

AU - Amaddeo, Giuliana

AU - Regnault, Hélène

AU - de Martin, Eleonora

AU - Sempoux, Christine

AU - Navale, Pooja

AU - Shinde, Jayendra

AU - Bacchuwar, Ketan

AU - Westerhoff, Maria

AU - Lo, Regina Cheuk Lam

AU - Sebbagh, Mylène

AU - Guettier, Catherine

AU - Lequoy, Marie

AU - Komuta, Mina

AU - Ziol, Marianne

AU - Paradis, Valérie

AU - Shen, Jeanne

AU - Caruso, Stefano

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - cancer

KW - cholangiocarcinoma

KW - combined hepatocellular-cholangiocarcinoma

KW - hepatocellular carcinoma

KW - liver

KW - nestin

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U2 - 10.1016/j.jhep.2022.07.019

DO - 10.1016/j.jhep.2022.07.019

M3 - Article

C2 - 35987274

AN - SCOPUS:85141295058

SN - 0168-8278

VL - 77

SP - 1586

EP - 1597

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 6

ER -

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

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