Histopathological characteristics of glutamine synthetase-positive hepatic tumor lesions in a mouse model of spontaneous metabolic syndrome (TSOD mouse)

Takahashi,Tetsuyuki; Nishida,Takeshi; Baba,Hayato; Hatta,Hideki; Imura,Johji; Sutoh,Mitsuko; Toyohara,Syunji; Hokao,Ryoji; Watanabe,Syunsuke; Ogawa,Hirohisa; Uehara,Hisanori; Tsuneyama,Koichi

doi:10.3892/mco.2016.924

Histopathological characteristics of glutamine synthetase-positive hepatic tumor lesions in a mouse model of spontaneous metabolic syndrome (TSOD mouse)

Authors:
- Tetsuyuki Takahashi
- Takeshi Nishida
- Hayato Baba
- Hideki Hatta
- Johji Imura
- Mitsuko Sutoh
- Syunji Toyohara
- Ryoji Hokao
- Syunsuke Watanabe
- Hirohisa Ogawa
- Hisanori Uehara
- Koichi Tsuneyama
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Affiliations: Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Tokushima 770‑8503, Japan, Department of Diagnostic Pathology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Toyama, Toyama 930‑0194, Japan, Institute for Animal Reproduction, Kasumigaura, Ibaraki 300‑0134, Japan
Published online on: June 9, 2016 https://doi.org/10.3892/mco.2016.924
Pages: 267-270
Copyright: © Takahashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

We previously reported that Tsumura-Suzuki obese diabetic (TSOD) mice, a polygenic model of spontaneous type 2 diabetes, is a valuable model of hepatic carcinogenesis via non‑alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). One of the characteristics of tumors in these mice is the diffuse expression of glutamine synthetase (GS), which is a diagnostic marker for hepatocellular carcinoma (HCC). In this study, we performed detailed histopathological examinations and found that GS expression was diffusely positive in >70% of the hepatic tumors from 15-month-old male TSOD mice. Translocation of β-catenin into nuclei with enhanced membranous expression also occurred in GS‑positive tumors. Small lesions (<1 mm) in GS‑positive cases exhibited dysplastic nodules, with severe nuclear atypia, whereas large lesions (>3 mm) bore the characteristics of human HCC, exhibiting nuclear and structural atypia with invasive growth. By contrast, the majority of GS‑negative tumors were hepatocellular adenomas with advanced fatty change and low nuclear grade. In GS-negative tumors, loss of liver fatty acid‑binding protein expression was observed. These results suggest that the histological characteristics of GS‑positive hepatic tumors in TSOD mice resemble human HCC; thus, this model may be a useful tool in translational research targeting the NAFLD̸NASH‑HCC sequence.

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