A Subset of Intrahepatic Cholangiocarcinomas Express Albumin RNA as Detected by In Situ Hybridization

Intrahepatic cholangiocarcinomas (ICCs) show morphologic diversity, ranging from tumors composed of nonmucinous small ducts to mucin-producing large duct tumors to tumors with mixed hepatocellular carcinoma features. Diagnosing ICCs can be difficult, especially on biopsy, not only because of the morphologic diversity, but also because metastatic tumors are often in the differential diagnosis. Recently, branched DNA-based albumin RNA in situ hybridization (ISH) has been shown to be a potential sensitive and specific marker for ICC with 99% sensitivity. Using a different RNA ISH technology, we evaluated the expression of albumin RNA ISH in ICC. We performed RNA ISH for albumin using RNAscope on 43 ICCs in a triplicate tissue microarray. Albumin RNA ISH was positive in 18 of 43 (42%) ICCs. Five of the 6 (83%) combined hepatocellular carcinoma-CC were positive in the CC component. None of the tumors with mucin production were positive (0/9). In our cohort, albumin RNA ISH showed a sensitivity of 42% in ICCs, supporting the morphologic diversity of ICCs. Albumin RNA ISH does not appear to be a highly sensitive marker for ICC and hence cannot be used as a stand-alone marker for ICC.