Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Radiology. 2010 Jun;255(3):824-33. doi: 10.1148/radiol.10091557.
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.
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 Scheffé post hoc test.
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.
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.
研究肝细胞癌（HCC）在钆塞酸增强肝胆期磁共振（MR）图像上增强的机制，并对增强后的 HCC 进行特征描述。
本回顾性研究经机构审查委员会批准，并获得了切除标本用于研究的患者知情同意。对 25 例（20 名男性，5 名女性；平均年龄 68 岁；范围，49-82 岁）接受手术切除的 27 个富血管性 HCC 患者的 MR 图像进行定量研究，这些 HCC 在钆塞酸增强 MR 图像上呈肝细胞摄取性增强。结果与免疫组织化学染色结果进行相关性分析，以检测用于检测窦状隙转运蛋白（OATP）1B1（OATP1B1）和/或 OATP1B3（OATP1B1 和/或 -1B3）的表达、用于检测管腔膜转运蛋白多药耐药相关蛋白 2（MRP2）的表达以及肿瘤内胆汁积聚的结果进行相关性分析。采用学生 t 检验和 Scheffé 事后检验进行统计学分析。
结合 OATP1B1 和/或 -1B3 表达阳性（O+），两种 MRP2 表达模式导致高增强：表达减少（M-，n=3）和假腺管腔膜表达增加（M+[P]，n=3）。无 OATP1B1 和/或 -1B3 表达的结节（O-，n=13）和 O+但仅在管腔表达 MRP2 增加的结节（M+[C]，n=8）的增强明显低于前两种表达模式（O+/M-组与 O-组，P=0.002；O+/M-组与 O+/M+[C]组，P=0.047；O+/M+[P]组与 O-组，P<0.001；O+/M+[P]组与 O+/M+[C]组，P<0.001）。有胆汁色素（n=12）的结节增强明显更高（P=0.004）；所有五个增强超过相邻肝实质的结节（一个高分化 HCC，四个中分化 HCC）均含有胆汁色素。
高肝细胞摄取性增强是由转运体的表达模式引起的，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。具有钆塞酸增强的 HCC 的特征是肿瘤内胆汁积聚。
