Abstract 3878: Differential expression of cancer stem cell markers and their clinicopathological features in hepatocellular carcinoma patients with different etiologies
Authors: Kogiso Tomomi , Hashimoto Etsuko , Kodama Kazuhisa , Tobari Maki , Matsushita Noriko , Torii Nobuyuki , Taniai Makiko , Tokushige Katsutoshi , Shiratori Keiko 
Published: May 2015

Aim: Some pluripotent genes and epithelial cell adhesion molecule (EpCAM) have been reported as cancer stem cell markers in hepatocellular carcinoma (HCC). Nanog was recently reported to regulate self-renewal of cancer stem cells though the insulin-like growth factor pathway in HCC. However, the expression status of the pluripotent stem cell genes and their clinicopathological significance in HCC from different etiologies remain unexplored. Here, we compared the expression status of stem cell markers in HCCs derived from hepatitis C virus (HCV)-related liver disease and from nonalcoholic steatohepatitis (NASH), and also determined the clinical characteristics of Nanog-positive HCCs in NASH patients.

Methods: Resected tissues from 21 NASH-related HCC (NASH-HCC) patients with histologically proven steatohepatitis and 24 HCV-related HCC (HCV-HCC)CV-HCC)HCV patients were analyzed with all patients' written informed consent. The NASH group was defined as patients who consumed less than 20 g/day of alcohol. The expression status of Nanog, Oct4, Sox9, and EpCAM were determined by immunohistochemistry. The clinicopathological features of Nanog-positive NASH-HCC patients were analyzed.

Results: 1) Nanog was strongly expressed in 14.3/8.3% of NASH-HCC/HCV-HCC patients, and in 66.7/25% of noncancerous tissues of NASH/HCV (p&lt;0.05). Strong positive expression (defined as a positive area of over 50% of the examined tissues) was observed in most in NASH-HCC cases. Nanog-positive HCC patients showed no expression of EpCAM, and were Oct4-positive in 50% of cases and Sox9-positive in 75%. 2) EpCAM was strongly expressed in 5.0/8.3% of NASH-HCC/HCV-HCC, and in 10/41.7% of noncancerous tissues of NASH/HCV (p&lt;0.05). EpCAM-positive HCC patients showed no expression of Nanog, Oct4, or Sox9. 3) The expression of Sox9 was more dominant in noncancerous tissues in both NASH and HCV patients. 4) In NASH-HCC, Nanog-positive patients showed a significantly higher indocyanine green retention rate at 15 min (ICG-R15), were more obese, and showed advanced fibrosis of noncancerous tissues.

Conclusions: The expression status of stem cell markers differed between NASH- and HCV-related liver diseases. The expression of Nanog and EpCAM in HCC were mutually exclusive and their expression in noncancerous liver tissues may be an independent risk factor in NASH- and HCV-related HCCs, respectively.

Citation Format: Tomomi Kogiso, Etsuko Hashimoto, Kazuhisa Kodama, Maki Tobari, Noriko Matsushita, Nobuyuki Torii, Makiko Taniai, Katsutoshi Tokushige, Keiko Shiratori. Differential expression of cancer stem cell markers and their clinicopathological features in hepatocellular carcinoma patients with different etiologies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3878. doi:10.1158/1538-7445.AM2014-3878