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Claudins and tricellulin in fibrolamellar hepatocellular carcinoma

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Abstract

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.

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Acknowledgments

This work was supported by grants ETT-089/2009 by the Hungarian Ministry of Health and OTKA T 75468 by the Hungarian National Scientific Research Fund.

Conflict of interest

The authors have no financial relationship with the organizations that sponsored the research. The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 2nd Department of Pathology, Semmelweis University, Üllői út 93, 1091, Budapest, Hungary

    Attila Patonai, Boglárka Erdélyi-Belle, Anna Korompay, Áron Somorácz, Gábor Lotz, András Kiss & Zsuzsa Schaff

  2. Institute of Pathology, University Clinic Heidelberg, Ruprecht-Karls University, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany

    Beate K. Straub & Peter Schirmacher

  3. First Institute of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085, Budapest, Hungary

    Ilona Kovalszky

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  1. Attila Patonai
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Correspondence to Zsuzsa Schaff.

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András Kiss and Zsuzsa Schaff equally contributed to this work.

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Patonai, A., Erdélyi-Belle, B., Korompay, A. et al. Claudins and tricellulin in fibrolamellar hepatocellular carcinoma. Virchows Arch 458, 679–688 (2011). https://doi.org/10.1007/s00428-011-1077-y

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