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Molecular Characteristics of Fibrolamellar Hepatocellular Carcinoma

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Pathology & Oncology Research

Abstract

Fibrolamellar hepatocellular carcinoma (FLC) occurs in non-cirrhotic liver and the etiopathogenesis is still obscure. Both hepatocellular and cholangiocellular markers are expressed in the tumor, however, molecular alterations and altered pathways playing role in the tumor pathogenesis are not clearly identified. The purpose of the present study was to compare the expression level of EGFR, syndecan-1 and ß-catenin in FLC, conventional hepatocellular carcinoma (cHCC) and cholangiocellular carcinoma (CCC) and to investigate the possibility of mutation both in EGFR and K-RAS. Eight FLCs were compared with 7 cHCCs, 7 CCCs and 5 normal liver samples. Cytokeratins 7, 8, 18, 19, HepPar1 (HSA), EGFR, syndecan-1 (CD138) and ß-catenin were detected by immunohistochemistry. In addition EGFR, ß-catenin and syndecan-1 were evaluated by digital morphometry and K-RAS, EGFR mutations in FLC cases using paraffin-embedded samples. All FLCs were positive for HepPar1 (HSA) and cytokeratins 7, 8, 18, but negative for cytokeratin 19 by immunohistochemistry. EGFR was significantly overexpressed in all three tumor types, being highest in FLCs (p = 0,0001). EGFR, K-RAS mutation analyses revealed no mutations in exons studied in FLCs. Our findings proved that expression of EGFR is higher in FLC than in other types of primary malignant hepatic tumors and no K-RAS mutation can be detected, so FLC is a good candidate for anti-EGFR treatment.

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Acknowledgement

This work was supported by grants ETT-089/2009 by the Hungarian Ministry of Health, OTKA T 75468 by the Hungarian National Scientific Research Fund, and TÁMOP 4.2.1.B-09/1/KMR-2010-0001 by the National Development Agency of Hungary.

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Authors and Affiliations

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

    Attila Patonai, Boglárka Erdélyi-Belle, Anna Korompay, Áron Somorácz, Péter Törzsök, Tamás Barbai, Erzsébet Rásó, Gábor Lotz, Zsuzsa Schaff & András Kiss

  2. First Institute of Pathology and Experimental Cancer Research, Semmelweis University Budapest, Budapest, Hungary

    Ilona Kovalszky

Authors
  1. Attila Patonai
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  2. Boglárka Erdélyi-Belle
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  3. Anna Korompay
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  4. Áron Somorácz
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  5. Péter Törzsök
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  6. Ilona Kovalszky
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  7. Tamás Barbai
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  8. Erzsébet Rásó
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  9. Gábor Lotz
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  10. Zsuzsa Schaff
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  11. András Kiss
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Corresponding author

Correspondence to Zsuzsa Schaff.

Additional information

Zsuzsa Schaff and András Kiss equally contributed

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Patonai, A., Erdélyi-Belle, B., Korompay, A. et al. Molecular Characteristics of Fibrolamellar Hepatocellular Carcinoma. Pathol. Oncol. Res. 19, 63–70 (2013). https://doi.org/10.1007/s12253-012-9558-0

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  • DOI: https://doi.org/10.1007/s12253-012-9558-0

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