Complementary roles of β-catenin and glutamine synthetase immunostaining in diagnosis of chemotherapy-treated and untreated hepatoblastoma

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.