Albumin mRNA and filamin-A are helpful for differentiating intrahepatic cholangiocarcinoma from extrahepatic origins

Abstract Background: The differential diagnosis of intrahepatic cholangiocarcinomas (iCCAs) from metastatic adenocarcinomas from organs adjacent to the liver is difficult due to histopathological similarity and a lack of specific markers. This study evaluates the performance of albumin mRNA in situ hybridization (ISH) and immunohistochemistry (IHC) of filamin-A and cytokeratin 19 (CK19) for differential diagnosis.Methods: A total of 181 iCCAs and 116 adenocarcinomas from extrahepatic organs (30 gallbladder, 28 pancreas, and 58 stomach) were collected, and albumin ISH and IHC for filamin-A and CK19 were performed. The sensitivity, specificity, and the area under the curve (AUC) on the receiver operating characteristic (ROC) curve analysis of each marker were evaluated for the diagnosis of iCCA over extrahepatic adenocarcinoma.Results: Albumin ISH showed 23.2% sensitivity and 100% specificity for iCCAs, including both the small-duct and large-duct types. The expression of filamin-A and CK19 in albumin ISH-negative iCCAs was compared with that in extrahepatic adenocarcinomas. Filamin-A showed 71.1% sensitivity, 87.5% specificity, and 0.79 AUC on the ROC in small-duct-type iCCAs, whereas it had 27.5% sensitivity, 87.5% specificity, and 0.58 AUC on the ROC in large-duct-type iCCAs. CK19 showed 87.9% sensitivity, 59.4% specificity, and 0.74 AUC on the ROC in large-duct-type iCCAs, whereas it had 44.7% sensitivity, 59.4% specificity, and 0.52 AUC on the ROC in small-duct-type iCCAs.Conclusion: Albumin ISH and IHC for filamin-A and CK19 showed distinct expression patterns according to iCCA type. Albumin ISH positivity supports the possibility of iCCA, and filamin-A IHC is helpful for differentiating small-duct-type iCCA from extrahepatic adenocarcinomas.