Abstract
Hepatocyte nuclear factor-1beta (HNF-1B) is involved in the hepatobiliary specification of hepatoblasts to cholangiocytes during liver development, and is strongly expressed throughout adult biliary epithelium. The aim of this study was to examine the expression of HNF-1B in different pathologic subtypes of primary liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (ICC), and the relationship between HNF-1B expression, clinicopathological features and prognosis. We retrospectively investigated 2 cohorts of patients, including 183 HCCs and 69 ICCs. The expression of HNF-1B was examined by immunohistochemistry. We found that HNF-1B expression was associated with pathological subtype of primary tumor, and HNF-1B expression in HCC tissue may be associated with the change of phenotype on recurrence. The HNF-1B expression was positively correlated with biliary/HPC (hepatic progenitor cell) markers expression. Further, multivariable analysis showed that HNF-1B expression was an independent prognostic factor for both overall survival and disease-free survival of HCC patients. However, no correlation between HNF-1B expression and survival was found in ICC patients. In summary, HCC with high HNF-1B expression displayed biliary phenotype and tended to show poorer prognosis. HNF-1B-positive malignant cells could be bipotential cells and give rise to both hepatocytic and cholangiocytic lineages during tumorigenesis.
Highlights
Cholangiocyte transcription factors such as hepatocyte nuclear factor-1beta (HNF-1B), called variant HNF1, is a homeodomain protein that plays an essential role in the liver-specific expression of many genes during differentiation and development[4]
We found that 15 of the 183 patients in cohort 1 were diagnosed as hepatocellular carcinoma (HCC) primarily at the first surgery while their recurrence changed to ICC in the subsequent surgeries
The main findings of our study were that Hepatocyte nuclear factor-1beta (HNF-1B) expression was associated with the pathologic subtype of primary liver cancer, and HNF-1B expression in HCC tissue may be associated with the change of phenotype on recurrence
Summary
Cholangiocyte transcription factors such as hepatocyte nuclear factor-1beta (HNF-1B), called variant HNF1 (vHNF1), is a homeodomain protein that plays an essential role in the liver-specific expression of many genes during differentiation and development[4]. Recent studies have shown that expression of HNF-1B is associated with higher risk of HCC. Studies reported that HCC with biliary differentiation, defined as having cytokeratin (CK) 19 positive cells, tended to show poorer surgical outcome[11]. We hypothesized that as a biliary marker, HNF-1B expression in primary liver cancer would be associated with HPC markers expression and predict a poorer outcome. To the best of our knowledge, the association between HNF-1B expression and the histopathologic type of liver cancers, and the prognostic value of HPC/biliary markers for HCC have not been studied in detail. We investigated HNF-1B expression in different pathologic subtypes of primary liver cancers, and the relationship between HNF-1B expression and HPC/biliary markers expression by means of immunohistochemistry
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
