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

JOURNAL OF HEPATOLOGY

卷:63

Article

Miltiadous, Oriana¹  Sia, Daniela^1,2  Hoshida, Yujin¹  Fiel, Maria Isabel¹  Harrington, Andrew N.¹  Thung, Swan N.¹  Tan, Poh Seng^1,3  Dong, Hui⁴  Revill, Kate¹  Chang, Charissa Y.¹  Roayaie, Sasan⁵  Byrne, Thomas J.⁶  Mazzaferro, Vincenzo²  Rakela, Jorge⁶  Florman, Sander¹  Schwartz, Myron¹  Llovet, Josep M.^1,7,8 

[1] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Recanati Miller Transplantat Inst,Mt Sinai Liver, Dept Med,Dept Pathol,Dept Surg Oncol,Div Liver Di, New York, NY 10029 USA

[2] Natl Canc Inst, Dept Surg, Gastrointestinal Surg & Liver Transplantat Unit, I-20133 Milan, Italy

[3] Natl Univ Hlth Syst, Univ Med Cluster, Div Gastroenterol & Hepatol, Singapore, Singapore

[4] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China

[5] Lenox Hill Hosp, Hofstra North Shore LIJ Sch Med, Liver Canc Program, New York, NY 10021 USA

[6] Mayo Clin, Div Hepatol, Phoenix, AZ USA

[7] Univ Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Liver Unit,Hosp Clin, Liver Canc Translat Res Lab,Barcelona Clin Liver, Catalonia, Spain

[8] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain

关键词: Gene expression;    Prognosis;    Stem cell;    Gene signature;    Survival;   

DOI  :  10.1016/j.jhep.2015.07.025

来源: Elsevier

【 摘 要 】

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 88 months, 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. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

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