Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR Imaging--correlation with molecular transporters and histopathologic features.
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.
Kitao
Azusa
A
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
Zen
Yoh
Y
Matsui
Osamu
O
Gabata
Toshifumi
T
Kobayashi
Satoshi
S
Koda
Wataru
W
Kozaka
Kazuto
K
Yoneda
Norihide
N
Yamashita
Tatsuya
T
Kaneko
Shuichi
S
Nakanuma
Yasuni
Y
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
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