Page 158 - ebook HCC

PROGRAMME
GENEVA, SWITZERLANDA, SWITZERLAND
EASL HCC SUMMITHCC SUMMIT
156 PROGRAMME AND ABSTRACTSAND ABSTRACTS GENEV EASL 157
157
156
FEBRUAR
FEBRUARY 13 - 16, 2014Y 13 - 16, 2014
Poster Board Number B45 Poster Board Number B46
MUTATIONS IN TP53, CTNNB1 AND PIK3CA LONGITUDINAL MRI-BASED RESPONSE
GENES IN HEPATOCELLULAR CARCINOMA MONITORING OF SORAFENIB TREATMENT
ASSOCIATED WITH HEPATITIS B AND HEPATITIS IN TRANSPLANTED VERSUS CHEMICALLY
C VIRUS INFECTIONS INDUCED RAT HCC

Franco M. Buonaguro , Luigi Buonaguro , Maria Lina Tornesello 1 Claudia M. Gross 1
1
1
1 Experimental Oncology, Istituto Nazionale Tumori Fond Pascale, Napoli, Italy 1 Radiology, Klinikum rechts der Isar, 81675 Munich, Germany
Corresponding author’s e-mail: irccsvir@unina.it Corresponding author’s e-mail: claudia_gross@gmx.de
Introduction: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death Introduction: Reliable non-invasive imaging methods are required to improve tumor
worldwide. Hepatocarcinogenesis is a multistep process mainly associated with persistent detection, characterization and therapy response monitoring. In HCC development and
infection with hepatitis B (HBV) or C (HCV) viruses and always involving the accumulation therapy, angiogenesis plays a major role, with the anti-angiogenic multikinase inhibitor
of genetic alterations over decades of chronic liver disease. Mutations in TP53 and sorafenib being the only approved systemic drug in advanced disease stages. To validate
CTNNB1 genes are considered the cancer drivers for HCC development with variable new non-invasive imaging methods, reliable model systems are required, faithfully
frequencies depending on the etiology. representing the human disease.
Aims: To evaluate the frequency and distribution of somatic mutations in TP53, CTNNB1 Aims: Goal of this work was the detection of sorafenib induced changes in tumor
and PIK3CA genes in HBV- and HCV-related HCCs.
BASIC POSTER ABSTRACTS Methodology: The comprehensive review evaluating somatic mutations in TP53 and transplanted (McA) HCC. BASIC POSTER ABSTRACTS
vascularisation by magnet resonance imaging (MRI) in two commonly employed
preclinical rat HCC model systems, diethylnitrosamine induced (DEN) and orthotopically
CTNNB1 genes in HBV- and HCV-related HCC cases has been carried out retrieving
cases available from the Catalog of Somatic Mutations in Cancer (COSMIC). Moreover,
Methodology: Multifocal DEN and McA rat HCC was established in 8 week old male
the mutational pattern of TP53 (exons 4-9) and CTNNB1 (exon 3) as well as PIK3CA (exon
Wistar rats and imaged by T2-weighted (T2w), dynamic contrast enhanced (DCE) and
9) genes in HCC from Southern Italy has been analyzed.
Results: The overall mutation frequency of TP53 and CTNNB1 was 33.3%, while hotspot diffusion weighted imaging (DWI) MRI. Imaging findings were correlated with histology.
Results: Volume analysis of DEN tumors displayed slower growth kinetics in treated (n=11)
variations in PIK3CA were completely absent. CTNNB1 mutations were significantly compared to untreated animals (n=6) (fold change difference=2.5, p=0.0009). In contrast
associated with young age (P=0.019) and moderately/poorly differentiated HCV-related McA tumors (n=3) grew faster compared to DEN tumors (fold change difference=3.2)
HCC (P=0.015). and no change in tumor volume was noted (n=4, fold change=3.3). In addition, perfusion
analyses showed higher values in untreated DEN (n=7; AUGC 90rel_mean =5.51) compared to
Conclusions: The results obtained in our Southern Italian HCC series show that somatic McA tumors (n = 3; AUGC 90rel_mean =1.94). Whereas DEN tumor perfusion (n=6; AUGC 90rel_
mutations in TP53 gene are similarly represented in HBV- (20%) and HCV-related (15.8%) mean =4.24) decreased in response to sorafenib, perfusion slightly increased in McA tumors
HCC cases and comparable to that previously reported among HCC cases from Northern (n=4, AUGC 90rel_mean =2.27). These differences in tumor perfusion were confirmed by
Italy (25%) and France (18%). Further studies are in progress and the extended analysis histological findings.
of genetic alterations will help to identify molecular markers for liver cancer prevention,
diagnosis and treatment of HBV and HCV-associated liver cancer. Conclusions: In summary, we were able to quantify tumor volume and perfusion changes
longitudinally in orthotopic rat HCC by MRI. Analyses revealed DEN tumors only, which
more closely resemble human HCC, responsive to sorafenib treatment. This finding
underlines the need for a careful model system selection and further validates the DEN
model system for future imaging and therapy response studies.