SnapShot: Hepatocellular Carcinoma

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Apr 14, 2014 - Advanced .... Andersen, J.B., Marquardt, J.U., Kleiner, D.E., Raggi, C., Kitade, M., Seo, D., Akita, H., Durkin, M.E., and Thorgeirsson, S.S. (2013).
SnapShot: Hepatocellular Carcinoma Jens U. Marquardt1 and Snorri S. Thorgeirsson2 Department of Medicine I, Johannes Gutenberg University of Mainz, 55131 Mainz, Germany 2 Laboratory of Experimental Carcinogenesis, CCR/NCI/NIH, Bethesda, MD 20892, USA

1

CLINICAL PROGRESSION OF LIVER CANCER

UNIFOCAL HCC

CELL TYPES OF ORIGIN FOR HCC Stemness

Arterial Phase

Stem cell

Bulk tumor cells Aggresive phenotype

Cancer stem cell Bipotential progenitor

Venous Phase

50 μm

Healthy liver

Chronic injury

Cirrhosis

PROGNOSTIC CLASSIFICATION

Molecular features

Clinical/ Morphological features

Favorable Outcome

Contrast MRI imaging illustrating typical hyperenhancement (wash-in) in the arterial phase followed by wash-out in the venous phase.

HCC

BCLC STAGING & THERAPY

Poor Outcome

ECOG 0–1 Well-preserved liver function

Poor liver function Poor differentiation CK19 positive

Smaller tumors No vascular invasion

Larger tumors Vascular invasion Extrahepatic spread

Genomic stability Telomerase repression

Genomic instability Telomerase reactivation

CTNNB1 mutation Polysomy 7

Loss of 8p Global hypomethylation

High miR-122 Low miR-517a

Low miR-122 High miR-517a

Expression of differentiation factors: HNF4α, CYPs

Stemness features: EpCAM, SALL4

Low Nault 5-gene score

High Nault 5-gene score

Beneficial subclass: G4-G5, S3

Adverse subclass: G1-G3, S1-2, proliferation, HA subtype

Beneficial metabolic profile

Adverse metabolic profile: stearoyl-CoA-desaturase activity, palmitate signaling

Genes: TERT Cumulative frequency: 20%-60%

Palliation

Early stage

CHILD A; PST 0; single