Fibrolamellar hepatocellular carcinoma is a subtype of
hepatocellular carcinoma occurring in non-cirrhotic liver at a younger age. The
tumor expresses both hepatocellular and cholangiocellular markers. Previously, our group described overexpression of
tight junction protein claudin 4 in
cholangiocellular carcinoma in contrast to
hepatocellular carcinoma. In the present study,
tight junction protein expressions were studied to possibly clarify bipotential lineage of
fibrolamellar hepatocellular carcinoma. Eleven fibrolamellar
hepatocellular carcinomas were compared with seven "conventional"
hepatocellular carcinomas, seven
cholangiocellular carcinomas, and five normal liver samples. By immunohistochemistry, all fibrolamellar
hepatocellular carcinomas were positive for HepPar1 and cytokeratins 7, 8, and 18, but negative for
cytokeratin 19.
Glypican-3 gave weak staining in two cases. Expression of
claudin 1 was lower, while that of
claudin 2 was higher in fibrolamellar
hepatocellular carcinomas than in other
tumors.
Claudins 3, 4, and 7 were not detectable in fibrolamellar
hepatocellular carcinomas as in the majority of "conventional"
hepatocellular carcinomas, contrary to high expression observed in
cholangiocellular carcinomas. Focal or diffuse
claudin 5 expression was detected in nine of 11 fibrolamellar
hepatocellular carcinomas contrary to other
tumors.
Tricellulin was significantly downregulated in all
tumors compared with normal liver. Our findings showed
claudins to exhibit specific expression patterns in fibrolamellar
hepatocellular carcinomas not observed in other primary liver
tumors, with unique
claudin 5 expression and pattern features similar to common
hepatocellular carcinoma, but different from
cholangiocellular carcinoma. This is the first report describing the loss of
tricellulin expression in human hepatic
tumors.