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European Radiology

, Volume 21, Issue 10, pp 2056–2066 | Cite as

The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging

  • Azusa KitaoEmail author
  • Osamu Matsui
  • Norihide Yoneda
  • Kazuto Kozaka
  • Rieko Shinmura
  • Wataru Koda
  • Satoshi Kobayashi
  • Toshifumi Gabata
  • Yoh Zen
  • Tatsuya Yamashita
  • Shuichi Kaneko
  • Yasuni Nakanuma
Gastrointestinal

Abstract

Objectives

To clarify the changes in organic anion-transporting polypeptide 8 (OATP8) expression and enhancement ratio on gadoxetic acid-enhanced MR imaging in hepatocellular nodules during multistep hepatocarcinogenesis.

Methods

In imaging analysis, we focused on 71 surgically resected hepatocellular carcinomas (well, moderately and poorly differentiated HCCs) and 1 dysplastic nodule (DN). We examined the enhancement ratio in the hepatobiliary phase of gadoxetic acid enhanced MR imaging [(1/postcontrast T1 value−1/precontrast T1 value)/(1/precontrast T1 value)], then analysed the correlation among the enhancement ratio, tumour differentiation grade and intensity of immunohistochemical OATP8 expression. In pathological analysis, we focused on surgically resected 190 hepatocellular nodules: low-grade DNs, high-grade DNs, early HCCs, well-differentiated, moderately differentiated and poorly differentiated HCCs, including cases without gadoxetic acid-enhanced MR imaging. We evaluated the correlation between the immunohistochemical OATP8 expression and the tumour differentiation grade.

Results

The enhancement ratio of HCCs decreased in accordance with the decline in tumour differentiation (P < 0.0001, R = 0.28) and with the decline of OATP8 expression (P < 0.0001, R = 0.81). The immunohistochemical OATP8 expression decreased from low-grade DNs to poorly differentiated HCCs (P < 0.0001, R = 0.15).

Conclusions

The immunohistochemical expression of OATP8 significantly decreases during multistep hepatocarcinogenesis, which may explain the decrease in enhancement ratio on gadoxetic acid-enhanced MR imaging.

Keywords

Hepatocellular carcinoma Hepatocarcinogenesis Magnetic resonance imaging Gadoxetic acid Organic anion transporting polypeptide 8 

Abbreviations

OATP

organic anion transporting polypeptide

MR

magnetic resonance

HCC

hepatocellular carcinoma

DN

dysplasic nodule

CT

computed tomography

SI

signal intensity

ROI

region of interest

HNF

hepatocyte nuclear factor

MRP

multidrug resistance associated protein

Notes

Acknowledgements

This work was supported in part by a Grant-in-Aid for Japanese Scientific Research (21591549) from the Ministry of Education, Culture, Sports, Science and Technology and by Health and Labor Sciences Research Grants for “Development of novel molecular markers and imaging modalities for earlier diagnosis of hepatocellular carcinoma”.

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Copyright information

© European Society of Radiology 2011

Authors and Affiliations

  • Azusa Kitao
    • 1
    Email author
  • Osamu Matsui
    • 1
  • Norihide Yoneda
    • 1
  • Kazuto Kozaka
    • 1
  • Rieko Shinmura
    • 1
  • Wataru Koda
    • 1
  • Satoshi Kobayashi
    • 1
  • Toshifumi Gabata
    • 1
  • Yoh Zen
    • 2
    • 4
  • Tatsuya Yamashita
    • 3
  • Shuichi Kaneko
    • 3
  • Yasuni Nakanuma
    • 2
  1. 1.Department of RadiologyKanazawa University Graduate School of Medical ScienceKanazawaJapan
  2. 2.Human PathologyKanazawa University Graduate School of Medical ScienceKanazawaJapan
  3. 3.GastroenterologyKanazawa University Graduate School of Medical ScienceKanazawaJapan
  4. 4.Institute of Liver StudiesKing’s College HospitalLondonUK

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