IMP3 expression is associated with poor outcome and epigenetic deregulation in intrahepatic cholangiocarcinoma
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Authors
Gao, YuanyuanYang, Michelle
Jiang, Zhong
Woda, Bruce A.
Mercurio, Arthur M.
Qin, Jianjie
Huang, Xinli
Zhang, Feng
Document Type
Journal ArticlePublication Date
2014-06-01Keywords
AdultAged
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
Intrahepatic
Cholangiocarcinoma
Outcome
Epigenetic
Methylation
Cancer Biology
Neoplasms
Pathological Conditions, Signs and Symptoms
Pathology
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Show full item recordAbstract
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.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 siteDOI
10.1016/j.humpath.2014.01.016Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26300PubMed ID
24745619Related Resources
Link to Article in PubMedDistribution License
http://creativecommons.org/licenses/by-nc-nd/3.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.humpath.2014.01.016
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/3.0/