title: The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, 920-8640, Japan. kitaoa@staff.kanazawa-u.ac.jp
authors.forename: Azusa
authors.initials: A
authors.lastname: Kitao
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
authors.forename: Norihide
authors.initials: N
authors.lastname: Yoneda
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kozaka
authors.forename: Rieko
authors.initials: R
authors.lastname: Shinmura
authors.forename: Wataru
authors.initials: W
authors.lastname: Koda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Gabata
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000473:pathology*; D003287:Contrast Media / Q000494:pharmacology*; D005260:Female; D019786:Gadolinium DTPA / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000175:diagnosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D029362:Organic Anion Transporters, Sodium-Independent / Q000096:biosynthesis*; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: D003287:Contrast Media; D029362:Organic Anion Transporters, Sodium-Independent; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA