Peritumoral ductular reaction is related to nuclear translocation of β-catenin in hepatocellular carcinoma

Increased peritumoral ductular reaction (DR) is related to poor prognosis in hepatocellular carcinoma (HCC) but the mechanism is unclear. Nuclear translocation of β-catenin is correlated with HCC metastasis and recurrence. Thus, we aim to explore whether there is a relationship between peritumoral DR and tumoral nuclear translocation of β-catenin in HCC. Hepatitis B virus (HBV)-related HCC patients (n = 120) were enrolled into this study from January 2003 to December 2007. Clinicopathological variables were collected and immunohistochemistry staining for cytokeratin 19 (CK19), proliferating cell nuclear antigen (PCNA), β-catenin, phosphorylated-Smad2 (PSmad2) and transforming growth factor-β1 (TGF-β1) were performed in tumor and/or peritumor liver tissues. Peritumoral DR is significantly correlated with local inflammation (P < 0.001), fibrosis (P < 0.001), tumor size (P = 0.006) and CK19 expression in the tumor (P = 0.005). More patients with peritumoral DR had nuclear accumulation of β-catenin than patients with mild peritumoral DR (37.50% vs. 14. 58%, P = 0.011). HCCs in the obvious DR group had stronger expression of PSmad2 than that in the mild DR group, and patients with nuclear translocation of β-catenin also had higher PSmad2 expression. In conclusion, increased peritumoral DR is related to tumoral nuclear translocation of β-catenin in HCC and enhanced action of TGF-β1 signaling may be involved in this relationship.