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Title: Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation.
Author: 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
Keywords: Expressió gènica
Cèl·lules mare
Càncer de fetge
Trasplantament hepàtic
Gene expression
Stem cells
Liver cancer
Hepatic transplantation
Issue Date: Dec-2015
Publisher: Elsevier
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: Journal of Hepatology, 2015, vol. 63, num. 6, p. 1368-1377
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ISSN: 0168-8278
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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