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Open Access Green as soon as Postprint is submitted to ZB.
Intratumor heterogeneity in hepatocellular carcinoma.
Clin. Cancer Res. 21, 1951-1961 (2015)
Purpose: Morphologic intratumor heterogeneity is well known to exist in hepatocellular carcinoma (HCC) but very few systematic analyses of this phenomenon have been performed. The aim of this study was to comprehensively characterize morphological intratumor heterogeneity in HCC. Also taken into account were well-known immunohistochemical markers and molecular changes in liver cells that are considered in proposed classifications of liver cell neoplasms or discussed as molecular therapeutic targets. Experimental Design: In HCC of 23 patients without medical pretreatment, a total of 120 tumor areas were defined. Analyzed were cell and tissue morphology, expression of the liver cell markers CK7, CD44, AFP, EpCAM and glutamine synthetase along with mutations of TP53 and CTNNB1, assayed by both Sanger and next generation sequencing. Results: Overall, intratumor heterogeneity was detectable in the majority of HCC cases (20/23, 87%). Heterogeneity solely on the level of morphology was found in 6/23 cases (26%), morphological heterogeneity combined with immunohistochemical heterogeneity in 9/23 cases (39%), and heterogeneity with respect to morphology, immunohistochemistry and mutational status of TP53 and CTNNB1 in 5/23 cases (22%). Conclusions: Our findings demonstrate that intratumor heterogeneity represents a challenge for the establishment of a robust HCC classification and may contribute to treatment failure and drug resistance in many cases of HCC.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Beta-catenin-mutations; Alpha-fetoprotein Expression; Tumor; Classification; Cancer; Cells; Markers; Genes; Liver; Hcc
ISSN (print) / ISBN
1078-0432
e-ISSN
1557-3265
Journal
Clinical Cancer Research
Quellenangaben
Volume: 21,
Issue: 8,
Pages: 1951-1961
Publisher
American Association for Cancer Research (AACR)
Publishing Place
Philadelphia
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Virology (VIRO)