Hepatocellular Carcinoma: Hepatocyte-selective Enhancement at Gadoxetic Acid-enhanced MR Imaging-Correlation with Expression of Sinusoidal and Canalicular Transporters and Bile Accumulation
Hepatocellular Carcinoma: Hepatocyte-selective Enhancement at Gadoxetic Acid-enhanced MR Imaging-Correlation with Expression of Sinusoidal and Canalicular Transporters and Bile Accumulation
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DOI：
10.1148/radiol.10091557
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发表时间：
2010-06-01
期刊：
影响因子：
19.7
通讯作者：
Tomoda, Kaname
中科院分区：
文献类型：
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作者：
Tsuboyama, Takahiro;Onishi, Hiromitsu;Tomoda, Kaname
目的：探讨钆塞酸增强肝胆相磁共振（MR）图像上肝细胞癌（HCC）的增强机制，并表征增强后的HCC。 材料和方法：这项回顾性研究得到了机构审查委员会的批准，并获得了患者对切除标本的研究使用的知情同意。对 25 名患者（20 名男性，5 名女性；平均年龄，68 岁；范围，49-82 岁）的 27 例切除的富血管性 HCC（1 例良好，13 例中度，13 例低分化）的 MR 图像进行了定量研究，这些 HCC 在钆塞酸增强 MR 图像上表现出肝细胞选择性增强，并将结果与正弦转运蛋白、有机阴离子的免疫组织化学染色结果相关联转运多肽 (OATP) 1B1 (OATP1B1) 和/或 OATP1B3（OATP1B1 和/或 -1B3），以及小管转运蛋白、多药耐药相关蛋白 2 (MRP2)，也与肿瘤中的胆汁积聚有关。使用Student t检验和Scheffe事后检验进行统计分析。结果：结合OATP1B1和/或-1B3阳性表达(O+)，MRP2表达的两种模式导致高度增强：假腺体管腔膜表达减少(M-，n = 3)和表达增加(M+[P]，n = 3)。没有 OATP1B1 和/或 -1B3 表达的结节 (O-, n = 13) 和仅在小管处与 MRP2 表达增加相关的 O+ 结节 (M+[C], n = 8) 诱导的增强显着低于之前描述的两种表达模式的结节 (O+/M- 组与 O- 组, P =.002; O+/M- 组与 O+/M+[C] 组, P = .047; O+/M+[P] 组与 O- 组，P < .001；O+/M+[P] 组与 O+/M+[C] 组，P< .001）。具有胆色素的结节 (n = 12) 显示出显着更高的强化 (P = .004)；所有5个结节（1个高分化HCC，4个中分化HCC）均比邻近肝实质增强，均含有胆色素。结论：转运蛋白的表达模式诱导肝细胞选择性增强，这可能导致钆塞酸在肿瘤细胞的细胞质或假腺管腔中积聚。钆塞酸增强的 HCC 的特征是肿瘤中胆汁积聚。
Purpose: To investigate the mechanism of enhancement of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced hepatobiliary phase magnetic resonance (MR) images and to characterize HCC thus enhanced.Materials and Methods: This retrospective study was approved by the institutional review board, and patient informed consent for research use of the resected specimen was obtained. MR images in 25 patients (20 men, five women; mean age, 68 years; range, 49-82 years) with 27 resected hypervascular HCCs (one well, 13 moderately, 13 poorly differentiated) that demonstrated hepatocyte-selective enhancement on gadoxetic acid-enhanced MR images, were quantitatively studied, and findings were correlated with results of immunohistochemical staining for a sinusoidal transporter, organic anion transporting polypeptide (OATP) 1B1 (OATP1B1) and/or OATP1B3 (OATP1B1 and/or -1B3), and a canalicular transporter, multidrug resistance-associated protein 2 (MRP2), and also with bile accumulation in tumors. Statistical analysis was performed with the Student t test and Scheffe post hoc test.Results: Combined with positive OATP1B1 and/or -1B3 expression (O+), two patterns of MRP2 expression contributed to high enhancement: decreased expression (M-, n = 3) and increased expression at the luminal membrane of pseudoglands (M+[P], n = 3). Nodules without OATP1B1 and/or -1B3 expression (O-, n = 13) and nodules with O+ associated with increased MRP2 expression only at the canaliculi (M+[C], n = 8) induced significantly lower enhancement than those with the two expression patterns described before (O+/M- group vs O- group, P =.002; O+/M- group vs O+/M+[C] group, P = .047; O+/M+[P] group vs O- group, P < .001; O+/M+[P] group vs O+/M+[C] group, P< .001). Nodules with bile pigment (n = 12) showed significantly higher enhancement (P = .004); all five nodules (one well differentiated HCC, four moderately differentiated HCCs), which were enhanced more than adjacent liver parenchyma, contained bile pigment.Conclusion: High hepatocyte-selective enhancement is induced by expression patterns of transporters, which may result in accumulation of gadoxetic acid in cytoplasm of tumor cells or in lumina of pseudoglands. An HCC with gadoxetic acid enhancement is characterized by bile accumulation in tumors.