Gadoxetic acid-enhanced magnetic resonance imaging reflects co-activation of β-catenin and hepatocyte nuclear factor 4α in hepatocellular carcinoma.

The aim of this study is to clarify the correlation of the co-activation of β-catenin and hepatocyte nuclear factor (HNF)4α with the findings of gadoxetic acid-enhanced magnetic resonance imaging (MRI), organic anion transporting polypeptide (OATP)1B3 expression, and histological findings in hepatocellular carcinoma (HCC). One hundred and ninety-six HCCs surgically resected from 174 patients were enrolled in this study. The HCCs were classified into four groups by immunohistochemical expression of β-catenin, glutamine synthetase (GS), and HNF4α: (i) β-catenin/GS (positive [+]) HNF4α (+); (ii) β-catenin/GS (+) HNF4α (negative [-]); (iii) β-catenin/GS (-) HNF4α (+); and (iv) β-catenin/GS (-) HNF4α (-). We compared the four groups in terms of the enhancement ratio on the hepatobiliary phase of gadoxetic acid-enhanced MRI, immunohistochemical organic anion transporter polypeptide (OATP)1B3 (a main uptake transporter of gadoxetic acid) expression and histological features, overall survival, and no recurrence survival. The Kruskal-Wallis test, Steel-Dwass multiple comparisons test, Fisher's exact test, and log-rank (Mantel-Cox) test were used for statistical analyses. Enhancement ratio on gadoxetic acid-enhanced MRI in HCC with β-catenin/GS (+) HNF4α (+) was significantly higher than those of the other three groups (P < 0.001). The OATP1B3 grade was also significantly higher in HCC with β-catenin/GS (+) HNF4α (+) (P < 0.001). Hepatocellular carcinoma with β-catenin/GS (+) HNF4α (+) showed the highest differentiation grade as compared to the other groups (P < 0.004). There were no significant differences in portal vein invasion, macroscopic growth pattern, or prognosis analyses between the four groups. Co-activation of β-catenin and HNF4α would promote OATP1B3 expression, and consequently higher enhancement ratio on gadoxetic acid-enhanced MRI and higher differentiation grade in HCC.