Changes in beta-catenin expression and activation during progression of primary sclerosing cholangitis predict disease recurrence

Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. We have previously demonstrated the importance of Wnt/beta -catenin signaling in mouse models of PSC. In this study, we wished to determine the clinical relevance of beta -catenin localization in patient samples. In livers explanted from patients diagnosed with PSC, the majority (12/16; 75%) lacked beta -catenin protein expression. Biopsies from patients post-transplant were classified as recurrent or non-recurrent based on pathology reports and then scored for beta -catenin activation as a function of immunohistochemical localization. Despite lack of statistical significance, patients with recurrent primary disease (n=11) had a greater percentage of samples with nuclear, transcriptionally active beta -catenin (average 58.8%) than those with no recurrence (n=10; 40.53%), while non-recurrence is correlated with beta -catenin staining at the cell surface (average 52.63% for non-recurrent vs. 27.34% for recurrent), as determined by three different methods of analysis. beta -catenin score and years-to-endpoint are both strongly associated with recurrence status (p=0.017 and p=0.00063, respectively). Finally, there was significant association between higher beta -catenin score and increased alkaline phosphatase, a marker of biliary injury and disease progression. Thus, beta -catenin expression and activation changes during the progression of PSC, and its localization may be a useful prognostic tool for predicting recurrence of this disease.

Automated summary

In this study, the clinical relevance of beta-catenin localization in patients with primary sclerosing cholangitis (PSC) was investigated. The results suggest that changes in beta-catenin expression and activation during the progression of PSC may serve as a useful prognostic tool for predicting disease recurrence.