Impact of stem cell marker expression on recurrence of TACE-treated hepatocellular carcinoma post liver transplantation

BMC Cancer

Research Article

Zhen Zeng¹  Jinyu Ren²  Brian Bridges²  Steven A Weinman²  Jie Zhao²  Josiah Cox³  Maura O’Neil⁴  Sean C Kumer⁵  Bashar Abdulkarim⁵  Timothy M Schmitt⁵ 

[1] Beijing 302th Hospital, 100039, Beijing, People’s Republic of China;Department of Internal Medicine, University of Kansas Medical Center, 66160, Kansas City, KS, USA;Department of Internal Medicine, University of Kansas Medical Center, 66160, Kansas City, KS, USA;Department of Microbiology, University of Kansas Medical Center, 66160, Kansas City, KS, USA;Department of Pathology, University of Kansas Medical Center, 66160, Kansas City, KS, USA;Department of Surgery, University of Kansas Medical Center, 66160, Kansas City, KS, USA;

关键词: Cancer stem cells;    EpCAM;    CD133;    CD90;    CD44;    Transarterial chemoembolization;   

DOI  :  10.1186/1471-2407-12-584

 received in 2012-07-27, accepted in 2012-11-30,  发布年份 2012

来源: Springer

【 摘 要 】

AbstractBackgroundLiver transplantation is the most effective therapy for cirrhosis-associated hepatocellular carcinoma (HCC) but its utility is limited by post-transplant tumor recurrence. Use of the Milan, size-based criteria, has reduced recurrence rate to less than 10% but many patients remain ineligible. Reduction of tumor size with local therapies has been used to “downstage” patients to allow them to qualify for transplantation, but the optimal criteria to predict tumor recurrence in these latter patients has not been established. The existence of a progenitor cell population, sometimes called cancer stem cells (CSCs), has been proposed to be one mechanism accounting for the chemotherapy resistance and recurrence of hepatocellular carcinoma. The aim of this study was to determine if transcatheter arterial chemoemolization (TACE) treated tumors have increased CSC marker expression and whether these markers could be used to predict tumor recurrence.MethodsFormalin fixed specimens were obtained from 39 HCC liver explants (23 with no treatment and 16 after TACE). Immunohistochemical staining was performed for EpCAM, CD44, CD90, and CD133. Staining for each marker was scored 0–3 by evaluating the number and intensity of positive tumor cells in 5 hpf of tumor in each specimen.ResultsTACE treated tumors displayed greater necrosis and fibrosis than non-TACE treated samples but there were no differences in morphology between the viable tumor cells of both groups. In TACE treated specimens, the staining of both EpCAM and CD133 was greater than in non-TACE specimens but CD44 and CD90 were the same. In the TACE group, the presence of high EpCAM staining was associated with tumor recurrence. Four of ten EpCAM high patients recurred while 0 of 6 EpCAM low patients recurred (P = 0.040). None of the other markers predicted recurrence.ConclusionHigh pre-transplant EpCAM staining predicted HCC recurrence. This suggests that the abundance of tumor cells with a CSC phenotype may be a critical factor in the likelihood of tumor recurrence in patients receiving liver transplantation after TACE.

【 授权许可】

Unknown   
© Zeng et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.