UMMS Affiliation

Department of Pathology; Department of Cancer Biology



Document Type



Adult; Aged; Bile Ducts, Intrahepatic; Blotting, Western; Cholangiocarcinoma; CpG Islands; DNA Methylation; Epigenesis, Genetic; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Promoter Regions, Genetic; RNA-Binding Proteins; Real-Time Polymerase Chain Reaction; Tumor Markers, Biological


IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an oncoprotein and a useful biomarker for a variety of malignancies and is associated with reduced overall survival of a number of them. IMP3 expression and its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have not been well investigated. The molecular mechanism underlying IMP3 expression in human cancer cells remains to be elucidated. Here we investigated IMP3 expression in ICC and adjacent nonneoplastic liver in 72 unifocal primary ICCs from a single institute by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction. IMP3 was specifically expressed in cancer cells but not in the surrounding normal tissue, and 59 (82%) of 72 ICCs were IMP3 positive by immunohistochemistry. Among 35 cases with lymphovascular invasion, 26 (74%) showed IMP3 positivity in lymph node metastases. IMP3 expression was significantly correlated with tumor size, pathological grade, metastasis, and clinical stage. Kaplan-Meier analysis demonstrated an inverse correlation between IMP3 expression and overall survival rate. Multivariate analysis revealed that IMP3 was the only risk factor associated with survival. To further explore the mechanism of IMP3 expression in cancers, we identified 2 CpG islands at IMP3 proximal promoter. Interestingly, the IMP3 promoter was almost completely demethylated in ICCs in contrast to densely methylated promoter in normal liver tissues. IMP3 expression is a useful biomarker for ICCs and can provide an independent prognostic value for patients with ICC. To our knoweldge, this is the first direct evidence of epigenetic deregulation of IMP3 in human cancer.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Rights and Permissions

Citation:Hum Pathol. 2014 Jun;45(6):1184-91. doi: 10.1016/j.humpath.2014.01.016. Epub 2014 Feb 6. Link to article on publisher's site

Related Resources

Link to Article in PubMed


IMP3, Intrahepatic, Cholangiocarcinoma, Outcome, Epigenetic, Methylation

PubMed ID


Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.