Complementary roles of β-catenin and glutamine synthetase immunostaining in diagnosis of chemotherapy-treated and untreated hepatoblastoma
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BACKGROUND/PURPOSE: This study aimed to evaluate the expression of β-catenin and its downstream target glutamine synthetase (GS) in hepatoblastoma (HB), and to evaluate the use of these two markers for diagnosing HB. METHODS: Eighteen untreated HBs and 22 HBs resected after neoadjuvant chemotherapy were analyzed using β-catenin and GS immunostaining. RESULTS: We detected nuclear β-catenin immunostaining in nearly all untreated HBs, including in fetal and embryonal epithelial components and in mesenchymal elements. We also observed diffuse GS expression in the epithelial component; however, it was frequently absent in embryonal and mesenchymal areas. In HBs resected after neoadjuvant chemotherapy, we recognized four histological patterns: fetal, hepatocellular-carcinoma-like, clear-cell, and normal-liver-like. All these patterns displayed diffuse GS expression. Fetal pattern showed diffuse nuclear β-catenin immunostaining. Nuclear β-catenin immunostaining was weak in the hepatocellular-carcinoma-like and clear-cell patterns. In normal-liver-like area, β-catenin expression was only located in the cell membrane. CONCLUSION: The results suggest that nuclear β-catenin expression and diffuse GS immunostaining are the hallmarks of HB. Although epithelial and mesenchymal components of HB display nuclear β-catenin staining, this expression is attenuated following chemotherapy-induced cell maturation. GS immunostaining is especially useful for the assessment of section margins after neoadjuvant chemotherapy.
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Ectopic Ctnnb1 activation by itself induces glutamine synthetase (Glul/GS) expression outside the endogenous GS expression normally observed in a two- to three-cell ring of hepatocytes around the central vein.
“In the liver, ectopic Ctnnb1 activation by itself induces glutamine synthetase (gene: Glul; protein: GS) expression outside of the endogenous GS expression normally observed in a two- to three-cell ring of hepatocytes around the central vein (CV) (28–32).”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [30]
The Introduction identifies GS as a downstream target of Wnt/β-catenin signaling, and the Results report diffuse GS staining in hepatoblastoma versus a perivenular pattern in nontumorous liver. But this immunostaining study does not establish that ectopic Ctnnb1 activation by itself induces GS; the Discussion allows for other mechanisms. Nor does it specify a two- to three-cell ring around the central vein. Page numbers were not available in our copy. (LLM, conf=0.86)
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Cited by
Sorted by citations
The origin of hepatocellular carcinoma depends on metabolic zonation
Guo, J., Liang, R., Chung, A., Li, Z., Li, B., Chen, E., Li, L., Wang, J., Hsieh, M.-H., Fang, I. X., et al. (2026) · Science · doi:10.1126/science.adv7129 · Cited by 24 · see citing works
- Authors
- Huang, W.-J., Tsai, J.-H., & Jeng, Y.-M.
- Affiliations
- Hsin Sheng College of Medical Care and Management (TW)
- National Taiwan University Hospital (TW)
- National Taiwan University (TW)
- Corresponding author
- Jeng, Yung-Ming
- Venue
- Journal of the Formosan Medical Association
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 116
- Issue
- 7
- Pages
- 549-553
- ISSN
- 0929-6646 (ISSN-L)
- OpenAlex
- W2542914250
- Cited by
- 38
- References
- 0
- Citations by year
- 2025: 3 · 2024: 1 · 2022: 26 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 3
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the Formosan Medical Association (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Keywords
- hepatoblastoma, β-catenin, glutamine synthetase, neoadjuvant chemotherapy, tumor markers, immunohistochemistry, cell maturation
- MeSH terms
- Glutamate-Ammonia Ligase, Humans, Immunohistochemistry, Liver Neoplasms, Biomarkers, Tumor, Hepatoblastoma, beta Catenin
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