Clinicopathologic characteristics of Wnt/β-catenin-deregulated hepatocellular carcinoma

Activation of Wnt/β-catenin pathway has been implicated as a mechanism of oncogenesis of hepatocellular carcinoma (HCC). CTNNB1 mutation, which encodes for β-catenin, has been found to be the most common underlying genetic alteration. In this study, we evaluated the frequency of aberrant β-catenin expression in our cohort of HCC cases and explored its correlation with clinicopathologic features.

Fifty-three cases of histologically proven HCC were included in this study. Nuclear expression (with or without cytoplasmic staining) in >5% tumor cells was regarded as positive for β-catenin. Comparison with clinicopathologic features of β-catenin-negative HCC cases (controls) was also done.

Nuclear β-catenin positivity was seen in 20 (37.7%) HCC cases. Median age was 60.5 years, and male-to-female ratio was 5.7:1. Alpha-fetoprotein (AFP) levels were normal in half of the patients (P = 0.03). Approximately 36.8% of hepatitis B virus-related, 50% of hepatitis C virus-related, and 35% of viral marker-negative HCC were positive for β-catenin. Median tumor size was 8.7 cm. Majority (53%) of β-catenin-positive HCCs were unicentric, and a significant proportion (65%) displayed a well-differentiated histology (P = 0.11). No specific histological type was associated with β-catenin positivity. Although not statistically significant, more patients (57%) with β-catenin-positive HCCs developed recurrence or progressive disease than β-catenin-negative patients (35%).

Aberrant β-catenin expression was seen in a substantial proportion of our HCC cases. β-catenin-positive HCC was associated with normal AFP levels, unicentric tumors, well-differentiated histology, and an unfavorable outcome.