Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.

BACKGROUND & AIMS: In patients with hepatocellular carcinoma (HCC), liver transplantation (LT) is an excellent therapy if tumor characteristics are within the Milan criteria. We aimed to define genomic features enabling to identify HCC patients beyond Milan criteria who have acceptable transplan...

ver descrição completa

Detalhes bibliográficos
Autores: Miltiadous, Oriana, Sia, Daniela, Hoshida, Yujin, Fiel, Maria Isabel, Harrington, Andrew N., Thung, Swan N., Seng Tan, Poh, Dong, Hui, Revill, Kate, Chang, Charissa Y., Roayaie, Sasan, Byrne, Thomas J., Mazzaferro, Vincenzo, Rakela, Jorge, Florman, Sander, Schwartz, Myron, Llovet i Bayer, Josep Maria
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2015
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/120383
Acesso em linha:https://hdl.handle.net/2445/120383
Access Level:acceso abierto
Palavra-chave:Expressió gènica
Cèl·lules mare
Càncer de fetge
Trasplantament hepàtic
Gene expression
Stem cells
Liver cancer
Hepatic transplantation
id ES_4ff7f3cee4ba3ba9d0c4963cadaa768d
oai_identifier_str oai:diposit.ub.edu:2445/120383
network_acronym_str ES
network_name_str España
repository_id_str
spelling Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.Miltiadous, OrianaSia, DanielaHoshida, YujinFiel, Maria IsabelHarrington, Andrew N.Thung, Swan N.Seng Tan, PohDong, HuiRevill, KateChang, Charissa Y.Roayaie, SasanByrne, Thomas J.Mazzaferro, VincenzoRakela, JorgeFlorman, SanderSchwartz, MyronLlovet i Bayer, Josep MariaExpressió gènicaCèl·lules mareCàncer de fetgeTrasplantament hepàticGene expressionStem cellsLiver cancerHepatic transplantationBACKGROUND & AIMS: In patients with hepatocellular carcinoma (HCC), liver transplantation (LT) is an excellent therapy if tumor characteristics are within the Milan criteria. We aimed to define genomic features enabling to identify HCC patients beyond Milan criteria who have acceptable transplant outcomes. METHODS: Among 770 consecutive HCC patients transplanted between 1990 and 2013, 132 had tumors exceeding Milan criteria on pathology and were enrolled in the study; 44% of the patients satisfied the 'up-to-7 rule' [7=sum of the size of the largest tumor and the number of tumors]. Explant tumors were assessed for genomic signatures and immunohistochemical markers associated with poor outcome. RESULTS: At a median follow-up of 88months, 64 patients had died and 45 recurred; the 5-year overall survival (OS) and recurrence rates were 57% and 35%, respectively. Cytokeratin 19 (CK19) gene signature was independently associated with recurrence [Hazard ratio (HR)=2.95, p<0.001], along with tumor size (HR=3.37, p=0.023) and presence of satellites (HR=2.98, p=0.001). S2 subclass signature was independently associated with poor OS (HR=3.18, p=0.001), along with tumor size (HR=5.06, p<0.001) and up-to-7 rule (HR=2.50, p=0.002). Using the presence of progenitor cell markers (either CK19 or S2 signatures) patients were classified into poor prognosis (n=58; 5-year recurrence 53%, survival 45%) and good prognosis (n=74; 5-year recurrence 19%, survival 67%) (HR=3.16, p<0.001 for recurrence, and HR=1.72, p=0.04 for OS). CONCLUSIONS: HCC patients transplanted beyond Milan criteria without gene signatures of progenitor markers (CK19 and S2) achieved survival rates similar as those within Milan criteria. Once prospectively validated, these markers may support a limited expansion of LT indications.Elsevier2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/120383Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1016/j.jhep.2015.07.025Journal of Hepatology, 2015, vol. 63, num. 6, p. 1368-1377https://doi.org/10.1016/j.jhep.2015.07.025cc-by-nc-nd (c) Elsevier, 2015http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1203832026-05-27T06:46:51Z
dc.title.none.fl_str_mv Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.
title Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.
spellingShingle Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.
Miltiadous, Oriana
Expressió gènica
Cèl·lules mare
Càncer de fetge
Trasplantament hepàtic
Gene expression
Stem cells
Liver cancer
Hepatic transplantation
title_short Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.
title_full Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.
title_fullStr Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.
title_full_unstemmed Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.
title_sort Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.
dc.creator.none.fl_str_mv Miltiadous, Oriana
Sia, Daniela
Hoshida, Yujin
Fiel, Maria Isabel
Harrington, Andrew N.
Thung, Swan N.
Seng Tan, Poh
Dong, Hui
Revill, Kate
Chang, Charissa Y.
Roayaie, Sasan
Byrne, Thomas J.
Mazzaferro, Vincenzo
Rakela, Jorge
Florman, Sander
Schwartz, Myron
Llovet i Bayer, Josep Maria
author Miltiadous, Oriana
author_facet Miltiadous, Oriana
Sia, Daniela
Hoshida, Yujin
Fiel, Maria Isabel
Harrington, Andrew N.
Thung, Swan N.
Seng Tan, Poh
Dong, Hui
Revill, Kate
Chang, Charissa Y.
Roayaie, Sasan
Byrne, Thomas J.
Mazzaferro, Vincenzo
Rakela, Jorge
Florman, Sander
Schwartz, Myron
Llovet i Bayer, Josep Maria
author_role author
author2 Sia, Daniela
Hoshida, Yujin
Fiel, Maria Isabel
Harrington, Andrew N.
Thung, Swan N.
Seng Tan, Poh
Dong, Hui
Revill, Kate
Chang, Charissa Y.
Roayaie, Sasan
Byrne, Thomas J.
Mazzaferro, Vincenzo
Rakela, Jorge
Florman, Sander
Schwartz, Myron
Llovet i Bayer, Josep Maria
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Expressió gènica
Cèl·lules mare
Càncer de fetge
Trasplantament hepàtic
Gene expression
Stem cells
Liver cancer
Hepatic transplantation
topic Expressió gènica
Cèl·lules mare
Càncer de fetge
Trasplantament hepàtic
Gene expression
Stem cells
Liver cancer
Hepatic transplantation
description BACKGROUND & AIMS: In patients with hepatocellular carcinoma (HCC), liver transplantation (LT) is an excellent therapy if tumor characteristics are within the Milan criteria. We aimed to define genomic features enabling to identify HCC patients beyond Milan criteria who have acceptable transplant outcomes. METHODS: Among 770 consecutive HCC patients transplanted between 1990 and 2013, 132 had tumors exceeding Milan criteria on pathology and were enrolled in the study; 44% of the patients satisfied the 'up-to-7 rule' [7=sum of the size of the largest tumor and the number of tumors]. Explant tumors were assessed for genomic signatures and immunohistochemical markers associated with poor outcome. RESULTS: At a median follow-up of 88months, 64 patients had died and 45 recurred; the 5-year overall survival (OS) and recurrence rates were 57% and 35%, respectively. Cytokeratin 19 (CK19) gene signature was independently associated with recurrence [Hazard ratio (HR)=2.95, p<0.001], along with tumor size (HR=3.37, p=0.023) and presence of satellites (HR=2.98, p=0.001). S2 subclass signature was independently associated with poor OS (HR=3.18, p=0.001), along with tumor size (HR=5.06, p<0.001) and up-to-7 rule (HR=2.50, p=0.002). Using the presence of progenitor cell markers (either CK19 or S2 signatures) patients were classified into poor prognosis (n=58; 5-year recurrence 53%, survival 45%) and good prognosis (n=74; 5-year recurrence 19%, survival 67%) (HR=3.16, p<0.001 for recurrence, and HR=1.72, p=0.04 for OS). CONCLUSIONS: HCC patients transplanted beyond Milan criteria without gene signatures of progenitor markers (CK19 and S2) achieved survival rates similar as those within Milan criteria. Once prospectively validated, these markers may support a limited expansion of LT indications.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/120383
url https://hdl.handle.net/2445/120383
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.jhep.2015.07.025
Journal of Hepatology, 2015, vol. 63, num. 6, p. 1368-1377
https://doi.org/10.1016/j.jhep.2015.07.025
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Elsevier, 2015
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Elsevier, 2015
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869407852516343808
score 15,300719

Registos relacionados