The Uptake Transporter OATP8 Expression Decreases During Multistep Hepatocarcinogenesis: Correlation with Gadoxetic Acid Enhanced MR Imaging

Azusa Kitao,Osamu Matsui,Norihide Yoneda,Kazuto Kozaka,Rieko Shinmura,Wataru Koda,Satoshi Kobayashi,Toshifumi Gabata,Yoh Zen,Tatsuya Yamashita,Shuichi Kaneko,Yasuni Nakanuma

European Radiology（2011）

Department of Radiology | Human Pathology | Gastroenterology

Cited 223|Views18

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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Key words

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

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