Hepatocellular Carcinoma: Signal Intensity at Gadoxetic Acid-enhanced MR Imaging-Correlation with Molecular Transporters and Histopathologic Features
Hepatocellular Carcinoma: Signal Intensity at Gadoxetic Acid-enhanced MR Imaging-Correlation with Molecular Transporters and Histopathologic Features
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DOI：
10.1148/radiol.10092214
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发表时间：
2010-09-01
期刊：
影响因子：
19.7
通讯作者：
Nakanuma, Yasuni
中科院分区：
文献类型：
--
作者：
Kitao, Azusa;Zen, Yoh;Nakanuma, Yasuni
目的：分析肝细胞癌（HCC）患者钆塞酸增强磁共振（MRI）肝胆相信号强度与肝细胞转运蛋白表达的相关性。材料与方法：获得伦理委员会批准和知情同意。40例手术切除的HCC根据钆塞酸增强MR成像肝胆期的结果分为低信号（n = 32）或等信号或高信号（n = 8）。在低信号和等信号或高信号HCC之间比较以下内容：钆塞酸增强MR成像的时间-信号强度曲线，聚合酶链反应（PCR）（22个结节）中7种转运蛋白（4种有机阴离子转运多肽[OATP]和3种多药耐药蛋白[MRP]）的表达水平，OATP 8免疫染色结果和组织学特征。结果：在时间-信号强度曲线上，低信号HCC在动态相后呈下降趋势，而等或高信号HCC在动态相后呈上升趋势。PCR结果显示，OATP 8（摄取转运蛋白）在低信号肝癌中的表达较低，而在等或高信号肝癌中的表达高于背景肝（P <0.001）。MRP 3（一种窦输出转运蛋白）的表达水平显示出与OATP 8相似的趋势（P < .001）。免疫组化显示OATP 8在低信号HCC中表达较弱，而在等或高信号HCC中表达持续（P <0.001）。在组织学检查中，等或高信号HCC比低信号HCC更常见假腺性增生伴胆栓（增殖模式P = 0.01，胆栓P = 0.006）。肝细胞癌在钆塞酸增强MRI肝胆期的增强率与OATP 8和MRP 3的表达水平呈正相关，表明钆塞酸被OATP 8摄取并由MRP 3排泄。(C)RSNA，2010年
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, 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).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. (C) RSNA, 2010