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Current status of imaging biomarkers predicting the biological nature of hepatocellular carcinoma

  • Norihide YonedaEmail author
  • Osamu Matsui
  • Satoshi Kobayashi
  • Azusa Kitao
  • Kazuto Kozaka
  • Dai Inoue
  • Kotaro Yoshida
  • Tetsuya Minami
  • Wataru Koda
  • Toshifumi Gabata
Invited Review
  • 34 Downloads

Abstract

Hepatocellular carcinoma (HCC) is heterogeneous in terms of its biological nature. Various factors related to its biological nature, including size, multifocality, macroscopic morphology, grade of differentiation, macro/microvascular invasion, bile duct invasion, intra-tumoral fat and molecular factors, and their value as prognostic imaging biomarkers have been reported. And recently, genome-based molecular HCC classification correlated with clinical outcome has been elucidated. The imaging biomarkers suggesting a less aggressive nature of HCC are smaller size, solitary tumor, smooth margin suggesting small nodular type with indistinct margin and simple nodular type with distinct margin, capsule, imaging biomarkers predicting early or well-differentiated grade, intra-tumoral fat detection, and low fluorodeoxyglucose (FDG) accumulation. The imaging biomarkers suggesting an aggressive HCC nature are larger size, multifocality, non-smooth margin suggesting simple nodular type with extranodular growth, confluent multinodular, and infiltrative type, imaging biomarkers predicting poor differentiation, macrovascular tumor thrombus, predicting microvascular invasion imaging biomarkers, bile duct dilatation or tumor thrombus, and high FDG accumulation. In the genome-based molecular classification, CTNNB-1 mutated HCC shows a less aggressive nature, while CK19/EpCAM positive HCC and macrotrabecular massive HCC show an aggressive one. Better understanding of these imaging biomarkers can contribute to devising more appropriate treatment plans for HCC.

Keywords

Hepatocellular carcinoma Biological nature Imaging biomarkers Genome-based molecular HCC classification 

Abbreviations

HCC

Hepatocellular carcinoma

T1WI 

T1 weighted image

MRI 

Magnetic resonance imaging

T2WI

 T2 weighted image

IM

Intrahepatic metastases

SN-IM

Small nodular type with indistinct margin

SN-DM

Simple nodular type with distinct margin

SN-EG

Simple nodular type with extranodular growth

CMN

Confluent multinodular type

HB phase

Hepatobiliary phase

DN

Dysplastic nodule

ADC

Apparent diffusion coefficient

DWI

Diffusion weighted image

FDG PET

Fluorodeoxyglucose positron emission tomography

OATP

Organic anion-transporting polypeptide

SPIO

Superparamagnetic iron oxide

HK

Hexokinase

GLUT1

Glucose transporter 1

G6Pase

Glucose-6-phosphatase

PPV

Positive predictive value

NPV

Negative predictive value

SUV

Standardized uptake values

AFP

α-Fetoprotein

PIVKA-II

Protein induced by Vitamin K absence or antagonists-II

HNF

Hepatocyte nuclear factor (HNF)

EMT

Epithelial–mesenchymal transformation

CK

Cytokeratin

EPCAM

Epithelial cell adhesion molecule

CTNNB1

Catenin beta 1

MTM-HCC

Macrotrabecular massive HCC

SH-HCC

Steatohepatitic HCC

Notes

Funding

This work received no grant funding.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to disclose with respect to this article.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Japan Radiological Society 2019

Authors and Affiliations

  • Norihide Yoneda
    • 1
    Email author
  • Osamu Matsui
    • 1
  • Satoshi Kobayashi
    • 2
  • Azusa Kitao
    • 1
  • Kazuto Kozaka
    • 1
  • Dai Inoue
    • 1
  • Kotaro Yoshida
    • 1
  • Tetsuya Minami
    • 3
  • Wataru Koda
    • 1
  • Toshifumi Gabata
    • 1
  1. 1.Department of RadiologyKanazawa University Graduate School of Medical SciencesKanazawaJapan
  2. 2.Department of Quantum Medical ImagingKanazawa University Graduate School of Medical SciencesKanazawaJapan
  3. 3.Department of RadiologyKanazawa Medical UniversityUchinadaJapan

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