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

  • Gastrointestinal
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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.

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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

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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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Authors and Affiliations

  1. Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, 920-8640, Japan

    Azusa Kitao, Osamu Matsui, Norihide Yoneda, Kazuto Kozaka, Rieko Shinmura, Wataru Koda, Satoshi Kobayashi & Toshifumi Gabata

  2. Human Pathology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

    Yoh Zen & Yasuni Nakanuma

  3. Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

    Tatsuya Yamashita & Shuichi Kaneko

  4. Institute of Liver Studies, King’s College Hospital, London, UK

    Yoh Zen

Authors
  1. Azusa Kitao
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  2. Osamu Matsui
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  3. Norihide Yoneda
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  12. Yasuni Nakanuma
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Correspondence to Azusa Kitao.

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Kitao, A., Matsui, O., Yoneda, N. et al. The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging. Eur Radiol 21, 2056–2066 (2011). https://doi.org/10.1007/s00330-011-2165-8

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  • DOI: https://doi.org/10.1007/s00330-011-2165-8

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