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Nestin as a Diagnostic and Prognostic Marker for Combined Hepatocellular-Cholangiocarcinoma.

Julien Calderaro 1 Luca Di Tommaso 2 Pascale Maillé 3 Aurélie Beaufrère 4 Cong Trung Nguyen 5 Lara Heij Viviane Gnemmi 6, 7 Rondell P. Graham Frédéric Charlotte 8 Suzanne Chartier Dominique Wendum 9, 10 Mukul Vij Daniela Allende Alba Diaz Carla Fuster Benjamin Rivière 11 Astrid Herrero 12, 11 Jérémy Augustin 13 Katja Evert Diego Francesco Calvisi Wei Qiang Leow Howard Ho Wai Leung Jan Bednarsch Emmanuel Boleslawski 14 Mohamed Rela Anthony Wing-Hung Chan Alejandro Forner 15 Maria Reig 16 Anaïs Pujals 17, 18 Loetitia Favre 17, 18 Manon Allaire 19 Olivier Scatton 9 Arnaud Uguen 20 Eric Trépo 21 Lukas Otero Sanchez Denis Chatelain 22 Myriam Remmelink Camille Boulagnon-Rombi 23 Céline Bazille 24, 25 Nathalie Sturm 26 Benjamin Menahem 27, 28 Eric Frouin 29 David Tougeron 29 Christophe Tournigand 17 Emmanuelle Kempf 30, 31 Haeryoung Kim 32 Massih Ningarhari 7, 33 Sophie Michalak-Provost Jakob Nikolas Kather Annette S. H. Gouw Purva Gopal Raffaele Brustia 18 Eric Vibert 34 Kornelius Schulze 35 Darius F. Rüther Sören A. Weidemann Rami Rhaiem 36 Jean-Charles Nault 37, 38, 39, 40 Alexis Laurent 41 Giuliana Amaddeo 18, 17 Hélène Regnault 17 Eleonora De Martin Christine Sempoux 42 Pooja Navale Jayendra Shinde 43 Ketan Bacchuwar 44 Maria Westerhoff 45 Regina Cheuk-Lam Lo Mylène Sebbagh Catherine Guettier 46, 47 Marie Lequoy 48, 9 Mina Komuta Marianne Ziol 49, 50 Valérie Paradis 51 Jeanne Shen Stefano Caruso 49, 52 
23 SiRMa - Laboratoire de Signalisation et Récepteurs Matriciels
MEDyC - Matrice extracellulaire et dynamique cellulaire - UMR 7369
Abstract : BACKGROUND AND 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 PLC. METHODS: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCC) and 221 intrahepatic cholangiocarcinomas (ICCA). 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 AUC of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from ICCA (AUC 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 a 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: Combined Hepatocellular-Cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) that lacks robust tissue biomarkers. We show in different clinical settings that Nestin immunohistochemical staining has a diagnostic value and 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.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03760904
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Soumis le : jeudi 25 août 2022 - 16:54:32
Dernière modification le : vendredi 9 septembre 2022 - 10:20:08

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Julien Calderaro, Luca Di Tommaso, Pascale Maillé, Aurélie Beaufrère, Cong Trung Nguyen, et al.. Nestin as a Diagnostic and Prognostic Marker for Combined Hepatocellular-Cholangiocarcinoma.. Journal of Hepatology, Elsevier, 2022, pp.S0168-8278(22)02983-X. ⟨10.1016/j.jhep.2022.07.019⟩. ⟨hal-03760904⟩

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