Page 167 - ebook HCC

164 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 165
FEBRUARY 13 - 16, 2014

INTEGRATED OMICS STUDIES TO DELINEATE TRANSLATIONAL TISSUE DIAGNOSTICS IN HCC
TUMOR HETEROGENEITY IN LIVER CANCER
Peter Schirmacher 1
1 Institute of Pathology, University Hospital, Heidelberg, Germany
Anuradha Budhu , Stephanie Roessler , Xin W. Wang 1
1
1
1 Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Corresponding author’s e-mail: peter.schirmacher@med.uni-heidelberg.de
Institute, Bethesda, United States
Corresponding author’s e-mail: xw3u@nih.gov
Introduction: Although there is no targeted therapy available for HCC so far, challenges
of molecular tissue diagnostics for predictive and differential diagnostic purposes are
already visible.
Liver cancer is extremely heterogeneous in its tumor biology and clinical presentation,
which impedes treatment options and poses a significant challenge to cancer management. Results: In differential diagnostics specific molecular markers support several important
Inter- and intra-tumor heterogeneity has been recognized, possibly emanating from the questions.
presence of cancer stem cells or selection by clonal evolution. To overcome this problem,
molecular-based technologies including genomic, transcriptomic and metabolomic 1. assessment of malignancy in highly differentiated hepatocellular neoplasms
profiling, have been applied to liver specimens to distinguish tumor subgroups, which 2. differentiation of hepatocellular carcinoma from mimics and mixed or unusual hepatic
allow for stratification of patients with greater homogeneity and can assist in molecular malignancies
re-staging. These various genome-based signatures also delineate critical gatekeepers of 3. identification of hepatocellular adenomas with higher malignant transformation
cancer initiation and progression which can be further honed by integrative genomics to potential
identify key driver genes and functionally linked networks capable of determining patient
prognosis or therapeutic outcome. Examples of biologically relevant molecular signatures These markers offer significant support for histological assessment and attempts are on
and drivers include those linked to metastasis, tumor recurrence, cancer stem cells, tumor the way to further improve the respective marker panels. Correct categorisation is essential
CLINICAL SPEAKERS ABSTRACTS molecular changes linked to different sets of cancer hallmarks which collectively occupy molecular markers may support definition of some rarer HCC subtypes in coordination CLINICAL SPEAKERS ABSTRACTS
metabolism and gender disparity. Furthermore, comparative genomics has revealed
for adequate therapeutic management. There are also recent indications that novel
that although signatures may share a common prognostic space, each carries unique
with histopathological characteristics. In the future we are likely to see an improved and
different tumor biological space. Integrative genomic approaches allow us to tease apart
combined histopathological and molecular subclassification of HCC, as witnessed in other
these differences, rooted in tumor heterogeneity, to identify critical biomarkers for cancer
malignancies, such as breast cancer and NSCLC.
diagnosis and clinically relevant therapeutic targets that represent convergent cancer
In predictive diagnostics several clinical trials are ongoing that require preemptive testing for
driving molecular nodes.
trial inclusion. These tests require either immunohistology (e.g. MET) or mutation analyses
(e.g. KRAS). In order to address trial and study center issues rational and comprehensive
testing and allocation measures (‘umbrella’ programs) are helpful. Furthermore, trial
associated analyses may help to identify patient subgroups responding (better) to therapy.
As trials may hopefully lead to novel approved therapies, concomitant, quality assured
testing has to be implemented in the diagnostic community and respective measures have
to be taken in parallel to clinical application (testing conditions, round robins etc.). These
measures, although only partly in place for liver cancer have been implemented in other
tumor entities and can be transferred to the HCC situation