title: Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR Imaging--correlation with molecular transporters and histopathologic features.
abstract: OBJECTIVE
  To analyze the correlation between signal intensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance (MR) imaging and the expression of hepatocyte transporters with histopathologic features in hepatocellular carcinoma (HCC).
  
  
  METHODS
  Institutional ethics committee approval and informed consent were obtained. Forty surgically resected HCCs were classified as hypointense (n = 32) or iso- or hyperintense (n = 8) on the basis of findings in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging. The following were compared between hypointense and iso- or hyperintense HCCs: the time-signal intensity curves at gadoxetic acid-enhanced MR imaging, the expression levels of seven transporters (four organic anion-transporting polypeptides [OATPs] and three multidrug-resistant proteins [MRPs]) at polymerase chain reaction (PCR) (for 22 nodules), results of immunostaining of OATP8, and histologic features. Statistical analysis (unpaired t test, Mann-Whitney test, chi(2) test, and Fisher exact test) was performed for each result.
  
  
  RESULTS
  On the time-signal intensity curves, hypointense HCCs showed a decreasing pattern, whereas iso- or hyperintense HCCs showed an increasing pattern after the dynamic phase. PCR revealed that expression of OATP8 (an uptake transporter) in hypointense HCCs was lower and that in iso- or hyperintense HCCs was higher than in background liver (P < .001). The expression level of MRP3 (a sinusoidal export transporter) showed a similar trend to that of OATP8 (P < .001). Immunostaining revealed that OATP8 expression was weak in hypointense HCCs, whereas it was sustained in iso- or hyperintense HCCs (P < .001). At histologic examination, a pseudoglandular proliferation pattern with bile plugs was more commonly observed in iso- or hyperintense HCCs than in hypointense HCCs (P = .01 for proliferation patterns and P = .006 for bile plugs).
  
  
  CONCLUSIONS
  The enhancement ratio of HCCs in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging positively correlated with expression levels of OATP8 and MRP3, indicating that gadoxetic acid is taken up by OATP8 and excreted by MRP3.
authors.affiliation: Department of Radiology, Human Pathology, and Gastroenterology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa 920-8640, Japan. kitao@rad.m.kanazawa-u.ac.jp
authors.forename: Azusa
authors.initials: A
authors.lastname: Kitao
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Gabata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Wataru
authors.initials: W
authors.lastname: Koda
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kozaka
authors.forename: Norihide
authors.initials: N
authors.lastname: Yoneda
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* / Q000378:metabolism* / Q000473:pathology; D016009:Chi-Square Distribution; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D018709:Statistics, Nonparametric
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029362:Organic Anion Transporters, Sodium-Independent; D012333:RNA, Messenger; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; C421209:SLCO1B3 protein, human; C073590:gadolinium ethoxybenzyl DTPA; C114462:multidrug resistance-associated protein 3