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Hepatocellular Carcinoma: Signal Intensity at Gadoxetic Acid–enhanced MR Imaging—Correlation with Molecular Transporters and Histopathologic Features

2010; Radiological Society of North America; Volume: 256; Issue: 3 Linguagem: Inglês

10.1148/radiol.10092214

1527-1315

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

Cancer, Lipids, and Metabolism

Purpose 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). Materials and 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, χ2 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). Conclusion 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. © RSNA, 2010 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10092214/-/DC1