UMMS Affiliation

Department of Pathology; Department of Cancer Biology

Publication Date

2014-06-01

Document Type

Article

Subjects

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

Disciplines

Cancer Biology | Neoplasms | Pathological Conditions, Signs and Symptoms | Pathology

Abstract

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.

Keywords

IMP3, Intrahepatic, Cholangiocarcinoma, Outcome, Epigenetic, Methylation

DOI of Published Version

10.1016/j.humpath.2014.01.016

Source

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

Journal/Book/Conference Title

Human pathology

Related Resources

Link to Article in PubMed

PubMed ID

24745619

Creative Commons License

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

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