Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Aug 27:5:13319.
doi: 10.1038/srep13319.

Overexpression Of Hepatocyte Nuclear Factor-1beta Predicting Poor Prognosis Is Associated With Biliary Phenotype In Patients With Hepatocellular Carcinoma

Dan-Dan Yu  1 , Ying-Ying Jing  1 , Shi-Wei Guo  1 , Fei Ye  1 , Wen Lu  1 , Quan Li  1 , Yu-Long Dong  1 , Lu Gao  1 , Yu-Ting Yang  1 , Yang Yang  1 , Meng-Chao Wu  2 , Li-Xin Wei  1
Affiliations

Overexpression Of Hepatocyte Nuclear Factor-1beta Predicting Poor Prognosis Is Associated With Biliary Phenotype In Patients With Hepatocellular Carcinoma

Dan-Dan Yu et al. Sci Rep. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. HNF-1B expression in primary tumor is associated with different pathologic types of recurrent tumor.
(A) Representative images in primary tumor and recurrent tumor of HE staining. (HCC-HCC: the non-pathological transition group. HCC-ICC: the pathological transition group, primary tumor was HCC while recurrent tumor changed to ICC) (sacle bar = 100 μm). (B) Representative images in primary tumor of HNF-1B immunostaining in 0, 1+, 2+ and 3 + (sacle bar = 100 μm). (C) The percentage of pathological transition cases in HNF-1B low expression group and HNF-1B high expression group. (D) The differences of HNF-1B expression percentage between non-pathological transition group and pathological transition group. (E) The significant differences of HNF-1B expression level between non-pathological transition group and pathological transition group (Mean±SD).
Figure 2
Figure 2. HNF-1B expression is associated with different pathologic types of primary tumor.
(A) HNF-1B immunohistochemical staining patterns in ICC tissues. Representative sections showing HNF-1B expression in 0, 1+, 2+ and 3 + (sacle bar = 100 μm). (B) The differences of HNF-1B expression percentage between HCC patients and ICC patients. (C) The significant differences of HNF-1B expression level between HCC patients and ICC patients (Mean±SD).
Figure 3
Figure 3. Expression of HNF-1B in HCC is positively correlated with expression of HPCs and biliary markers.
(A) Representative images of HPCs markers (EpCAM, OV6) and biliary markers (K7, K19) expression (sacle bar = 100 μm). (B) Representative images of double staining of HNF-1B and K7, K19 (sacle bar = 100 μm). (C) The HNF-1B expression is positively correlated with K7, K19, EpCAM, and OV6 expression. Spearman correlation analysis provides correlation coefficient (r) and P-value.
Figure 4
Figure 4. Kaplan-Meier analysis of HNF-1B expression in HCC patients.
HNF-1B low expression in HCC tissues was associated with prolonged overall survival (A) and disease-free survival (B). The P value calculated by the log-rank test is indicated.
Figure 5
Figure 5. HNF-1B expression in nontumor tissues is associated with PI-DR and DFS.
(A) Representative images of double staining of HNF-1B and K7 in ductular reaction cells of non-tumor tissue (sacle bar = 100 μm). (B) Representative images of HNF-1B expression in hepatocytes of non-tumor tissue. (sacle bar = 100 μm) (C) The sequential serial sections stained with K7 and PCNA (sacle bar = 100 μm). (D) HNF-1B expression in hepatocytes of non-tumor tissue is significantly correlated with PI-DR. Spearman correlation analysis provides correlation coefficient (r) and P-value. (E) HNF-1B low expression in hepatocytes of non-tumor tissues was associated with prolonged disease-free survival. The P value calculated by the log-rank test is indicated.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bosman F. T., C. F., Hruban R. H. & Theise N. D. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC (2010).
    1. Mittal S. & El-Serag H. B. Epidemiology of hepatocellular carcinoma: consider the population. Journal of clinical gastroenterology 47 Suppl, S2–6, 10.1097/MCG.0b013e3182872f29 (2013). - DOI - PMC - PubMed
    1. Jemal A. et al. Global cancer statistics. CA: a cancer journal for clinicians 61, 69–90, 10.3322/caac.20107 (2011). - DOI - PubMed
    1. Brimo F. et al. Hepatocyte nuclear factor-1beta expression in clear cell adenocarcinomas of the bladder and urethra: diagnostic utility and implications for histogenesis. Human pathology 42, 1613–1619, 10.1016/j.humpath.2011.01.007 (2011). - DOI - PubMed
    1. Horikawa Y. et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nature genetics 17, 384–385, 10.1038/ng1297-384 (1997). - DOI - PubMed

Publication types

MeSH terms

Substances