Correlation between CTNNB1 mutation status and tumour phenotype in hepatitis B virus-related hepatocellular carcinoma

Abstract

Aims: The frequency of CTNNB1 mutation, one of the most frequent genetic events in hepatocellular carcinoma (HCC), is lower in Asian countries and in hepatitis B virus (HBV)-related HCCs. In this study, we evaluated the prevalence and types of CTNNB1-mutation in HBV-related HCC and correlated the molecular status with the histomorphological and immunohistochemical features. Methods and results: A total of 108 consecutive cases of treatment-na & iuml;ve, surgically resected HBV-related HCCs were selected. Targeted sequencing for CTNNB1 exons 3, 7 and 8 was performed, and the results were correlated with the expression pattern of glutamine synthetase (GS), nuclear beta-catenin expression status and the histomorphological characteristics of the tumour. CTNNB1 mutations were identified in 13% of HBV-related HCCs; of these cases, mutations were found in D32-S37 (7%), T41 (4%) and S45 (2%) of exon 3. None of the HCCs demonstrated alterations in exons 7 and 8. CTNNB1 mutation was strongly associated with diffuse strong GS expression (P < 0.001), nuclear beta-catenin expression (P < 0.001) and the classic CTNNB1 morphology (P = 0.038). Diffuse strong GS expression was observed in 78.6% of the CTNNB1-mutated HCCs, and nuclear beta-catenin expression was identified in 64.3% of these cases. The classic CTNNB1 morphology was observed in 57% of all CTNNB1-mutated HCCs. Furthermore, programmed death-ligand 1 (PD-L1) was less frequently expressed in HCCs with classic CTNNB1 morphology. Conclusions: CTNNB1 mutation was observed in 13% of HBV-related HCCs in this Korean cohort, and was associated with diffuse strong GS expression, nuclear beta-catenin expression and classic CTNNB1 morphology.