Diagnostic and pathogenetic implications of the expression of hepatic transporters in focal lesions occurring in normal liver
Diagnostic and pathogenetic implications of the expression of hepatic transporters in focal lesions occurring in normal liver
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DOI：
10.1002/path.1852
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发表时间：
2005-12-01
影响因子：
7.3
通讯作者：
Roskams, TA
中科院分区：
文献类型：
--
作者：
Vander Borght, S;Libbrecht, L;Roskams, TA
肝细胞腺瘤和局灶性结节状增生(FNH)是肝脏良性肿瘤。这些病变和分化良好至中度的肝细胞癌的鉴别诊断通常很困难，但鉴于它们的治疗方法不同，这一点非常重要。虽然这两种类型的病变都与胆道树有关，但FNHs是胆汁淤积性的，而肝细胞腺瘤很少出现这种情况。这表明与腺瘤相比，肝细胞对胆汁成分的摄取和分泌是不同的。因此，我们利用实时定量RT-PCR和(半)定量免疫组织化学方法，研究了转运蛋白在非肝硬化性肝细胞腺瘤、不同类型FNH和中高分化肝细胞癌中的表达和定位，并与正常肝脏进行了比较。摄取转运蛋白OATP2/8(OATP1B1/3)在腺瘤中有少量或无实质表达，而在FNH中有强而弥漫表达。我们观察到基侧输出泵MRP3在腺瘤中的弥漫性实质表达，而在FNH中只有反应性胆管和邻近的淤胆肝细胞MRP3阳性。不典型FNH的MRP3/OATP2/8表达模式与腺瘤相似，提示两种类型的病变具有相关性。大多数肝细胞癌表现为一种或多种小管转运蛋白(MDR1、MDR3、BSEP)的表达降低。FNHs和腺瘤之间转运蛋白表达谱的差异很可能是重要的病理因素，并可能解释为什么只有FNHs具有胆汁淤积作用。非肝硬化性肝局灶性病变的每一种类型都有特定的转运蛋白表达模式，这一发现可能有助于通过成像或针吸活检确定正确的诊断。版权所有(C)2005年大不列颠和爱尔兰病理学会。作者：John Wiley&Sons，Ltd.
Hepatocellular adenoma and focal nodular hyperplasia (FNH) are benign liver tumours. The differential diagnosis of these lesions and of well- to moderately differentiated hepatocellular carcinomas is often difficult but is very important in view of their different treatment. Although neither type of lesion is connected to the biliary tree, FNHs are cholestatic, whereas this is rarely the case for hepatocellular adenomas. This suggests that hepatocellular uptake and secretion of bile constituents is different in FNHs compared to adenomas. We therefore evaluated the expression and localization of hepatic transporters in hepatocellular adenomas, different types of FNH and well- to moderately differentiated hepatocellular carcinomas in non-cirrhotic liver and compared them with normal liver, using real-time RT-PCR and (semi-)quantitative immunohistochemistry. The parenchymal expression of the uptake transporter OATP2/8 (OATP1B1/3) was minimal or absent in adenoma, while there was strong and diffuse expression in FNH. We observed diffuse parenchymal expression of the basolateral export pump MRP3 in adenomas, while only reactive bile ductules and adjacent cholestatic hepatocytes were MRP3-positive in FNH. The MRP3/OATP2/8 expression pattern of atypical FNHs resembled that of adenomas, suggesting that both types of lesion are related. Most hepatocellular carcinomas showed decreased expression of one or more of the canalicular transporters (MDR1, MDR3, BSEP). The differences in transporter expression profile between FNHs and adenomas are most likely pathogenetically important and may explain why only FNHs are cholestatic. The finding that each type of focal lesion in non-cirrhotic liver has a specific transporter expression pattern may be useful in the establishment of a correct diagnosis by imaging or on needle biopsy. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.