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目的:探讨白蛋白RNAscope原位杂交检测在肝细胞癌诊断及鉴别诊断中的价值。方法:选取上海交通大学医学院附属瑞金医院病理科2013年1月至2019年12月病理数据库中存档的152例肿瘤组织（包括肝细胞癌及组织形态与其相似的肿瘤）和33例不同部位肿瘤旁正常组织蜡块，制成组织芯片，使用RNAscope原位杂交法检测白蛋白mRNA的表达，观察并分析其表达情况。结果:除肝脏外，其他器官的正常组织中均未检测到白蛋白mRNA表达。肝细胞癌无论分化程度如何，无论原发性还是转移性，均表达白蛋白mRNA（阳性率100.0%，54/54），其中90.7%（49/54）呈弥漫强阳性。肝细胞癌免疫组织化学染色HepPar-1阳性率、Arg-1阳性率及HepPar-1或Arg-1两者之一阳性的阳性率分别为87.0%（47/54）、85.2%（46/54）及92.6%（50/54）。肝内胆管细胞癌及双表型肝细胞癌白蛋白mRNA阳性占比分别为7/15及9/10，前者呈局灶或异质性表达，而后者呈弥漫强阳性表达。肝样腺癌白蛋白mRNA阳性占比8/19，可呈弥漫或局灶性表达。1例胃低分化腺癌及1例转移性结肠腺癌局灶表达白蛋白mRNA。结论:白蛋白RNAscope原位杂交检测在肝细胞癌诊断及鉴别诊断中具有重要价值，将其与HepPar-1及Arg-1联合使用可以提高肝细胞癌诊断的灵敏度，而且根据其表达模式的不同对诊断具有不同的提示作用。“,”Objective:To investigate the utility of albumin RNAscope in situ hybridization in the diagnosis and differential diagnosis of hepatocellular carcinoma and its mimics.Methods:One hundred and fifty-two cases of hepatocellular carcinoma and its mimics and 33 cases of normal tissue were selected from the pathology database of the Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019. Tissue microarrays were constructed and RNAscope in situ hybridization was performed to detect the expression of albumin mRNA.Results:No albumin mRNA expression was detected in normal tissues except for the liver. All hepatocellular carcinoma regardless of its degree of differentiation and primary or metastatic nature had detectable albumin mRNA, with strong and diffuse staining in 90.7% (49/54) of cases. While the positive rate of HepPar-1, Arg-1 or one of them by immunohistochemistry was 87.0% (47/54), 85.2% (46/54) and 92.6% (50/54) respectively. The positive rates of albumin mRNA in intrahepatic cholangiocarcinoma and biphenotypic hepatocellular carcinoma were 7/15 and 9/10, respectively. The former showed focal or heterogeneous staining, while the latter showed strong and diffuse staining. The positive rate of hepatoid adenocarcinoma was 8/19, and the albumin expression could be diffuse or focal. Sporadic cases of poorly differentiated gastric adenocarcinoma and metastatic colon adenocarcinoma showed focal staining of albumin mRNA.Conclusions:Detection of albumin mRNA by RNAscope in situ hybridization is of great value for the diagnosis and differential diagnosis of HCC, and the sensitivity may be improved by combining with HepPar-1 and Arg-1. It also offers different diagnostic clues according to different expression patterns.