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Friemel, J.* ; Rechsteiner, M.P.* ; Frick, L.* ; Boehm, F.* ; Struckmann, K.* ; Sigg, M.* ; Moch, H.* ; Heikenwälder, M. ; Weber, A.*

Intratumor heterogeneity in hepatocellular carcinoma.

Clin. Cancer Res. 21, 1951-1961 (2015)
Verlagsversion DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Beta-catenin-mutations; Alpha-fetoprotein Expression; Tumor; Classification; Cancer; Cells; Markers; Genes; Liver; Hcc
Sprache englisch
Veröffentlichungsjahr 2015
Prepublished im Jahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 1078-0432
e-ISSN 1557-3265
Zeitschrift Clinical Cancer Research
Quellenangaben Band: 21, Heft: 8, Seiten: 1951-1961 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Verlagsort Philadelphia
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-551600-001
PubMed ID 25248380
DOI 10.1158/1078-0432.CCR-14-0122
WOS ID WOS:000352897200024
Erfassungsdatum 2014-09-26
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