We herein examined the immunohistochemical expression of 2 hepatocyte-specific transporters (bile salt export pump [BSEP] and multidrug-resistance protein 3 [MDR3]) in hepatocellular carcinomas (HCCs, n=54), intrahepatic cholangiocarcinomas (n=34), combined hepatocellular and cholangiocarcinomas (n=23), and hepatoid carcinomas originated from extrahepatic organs (n=27) to compare their diagnostic values with those of arginase-1 (ARG1) and hepatocyte paraffin-1 (HepPar-1). BSEP was expressed in 91% of HCCs and MDR3 in 83%. Although their sensitivities were slightly lower than those of ARG1 (96%) and HepPar-1 (93%), the 2 transporters appeared to be more specific for HCCs. ARG1 and HepPar-1 were expressed in intrahepatic cholangiocarcinomas (9% and 6%) and hepatoid carcinomas (22% and 44%, respectively), whereas BSEP and MDR3 were entirely negative in these neoplasms, except for 1 case of BSEP-positive hepatoid carcinoma of the esophagus. The highly specific expression of BSEP and MDR3 in hepatocytes was recapitulated in additional examinations of combined hepatocellular and cholangiocarcinomas, in which the expression of the transporters was restricted to morphologically hepatocellular areas. In contrast, ARG1 and HepPar-1 were also variably positive in areas of biliary or indeterminate differentiation. We also applied BSEP and MDR3 immunohistochemistry to 8 biopsy cases of poorly differentiated primary liver cancer, in which the original diagnosis was not conclusive. The diagnosis of HCC was retrospectively suggested in 2 cases expressing both BSEP and MDR3. In conclusion, given the highly specific expression of BSEP and MDR3 in HCCs, immunohistochemistry for these transporters will be useful not only for determining hepatocellular differentiation in primary liver cancers but also for discriminating HCCs from hepatoid carcinomas.
结果表明：91%的HCCs表达BSEP，83%的HCCs表达MDR3；与ARG1 (96%)和HepPar-1 (93%)相比，尽管它们的敏感性稍差，然而这两种转录蛋白对于HCCs的诊断更加特异。ARG1和HepPar-1在肝内胆管细胞癌中的表达分别为9%、6%，在肝样癌中的表达率分别为22%、44%；除了1例发生在食管的肝样癌BSEP阳性外，BSEP和MDR3在这些肿瘤中完全阴性。BSEP和MDR3在肝细胞癌中的高特异性表达，并且在混合性肝细胞和胆管细胞癌中，它们的表达局限在形态学为肝细胞癌的区域。相反，ARG1和HepPar-1在胆管或不确定分化的区域不定的阳性。
作者同时在8例分化差的原发性肝癌活检组织中检测了BSEP 和MDR3的表达，这些病例的最初诊断并不确定，2例同时表达BSEP 和MDR3，提示为HCC。