The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging
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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.
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.
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).
The immunohistochemical expression of OATP8 significantly decreases during multistep hepatocarcinogenesis, which may explain the decrease in enhancement ratio on gadoxetic acid-enhanced MR imaging.
KeywordsHepatocellular carcinoma Hepatocarcinogenesis Magnetic resonance imaging Gadoxetic acid Organic anion transporting polypeptide 8
organic anion transporting polypeptide
region of interest
hepatocyte nuclear factor
multidrug resistance associated protein
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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