The Diagnostic Utility of the Keratin Profiles of Hepatocellular Carcinoma and Cholangiocarcinoma

Abstract

A total of 32 hepatocellular carcinomas (HCC), 10 cholangiocarcinomas (CC), one combined HCC-CC, and 10 adenocarcinomas metastatic to the liver were studied immunohistochemically using AE1 and Cam 5.2, monoclonal antikeratin antibodies with different specificities. AE1 recognizes keratins with molecular weights of 56.5, 50/50', 48, and 40 kd (keratin nos. 10, 14, 15, 16, and 19, according to Moll's catalog), and labels many epithelia, including bile duct epithelium, but not hepatocytes. Both biliary epithelium and hepatocytes are stained by Cam 5.2, which reacts with keratins of molecular weights 50, 43, and 39 kd (corresponding to keratin nos. 8, 18, and 19). Tissues were formalin fixed, paraffin embedded, and a three-stage immunoperoxidase technique was employed. Of 32 pure HCCs, 29 were unreactive with AE1 yet were positive with Cam 5.2. The intensity and extent of immunostaining with Cam 5.2 did not correlate with tumor grade. In contrast to the HCCs, all 10 CCs and the 10 hepatic metastases were strongly positive with both AE1 and Cam 5.2. The combined HCC-CC was also labeled by both antibodies. We conclude that most HCCs express an immunohistochemical keratin profile identical to that of nonneoplastic hepatocytes, which differs from the keratin patterns of bile ducts, CCs, and metastatic adenocarcinomas from a variety of primary sites. These differences in immunoreactivity with antikeratin antibodies may prove useful in diagnostic surgical pathology.