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Chromogenic In Situ Hybridization Analysis of Epidermal Growth Factor Receptor Gene/Chromosome 7 Numerical Aberrations in Hepatocellular Carcinoma Based on Tissue Microarrays

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Pathology & Oncology Research

Abstract

Although Epidermal Growth Factor Receptor (EGFR) overexpression is observed frequently in hepatocellular carcinomas (HCC), specific gene deregulation mechanisms remain unknown. Our aim was to investigate the prognostic significance of the combined protein and gene/chromosome 7 numerical alterations. Using tissue microarray technology, thirty-five (n = 35) paraffin embedded histologically confirmed HCCs were cored and re-embedded in a paraffin block. Immunohistochemistry was performed for the determination of EGFR protein levels and evaluated by the performance of digital image analysis. Chromogenic in situ hybridization was also performed based on the use of EGFR gene and chromosome 7 centromeric probes, respectively. EGFR overexpression was observed in 26/35 (74.2%) cases and was correlated to the grade of the tumors and also to the history of the patients (p = 0.013, p = 0.036, respectively). Numerical alterations regarding gene and chromosome 7 were identified in 4/35 (11.4%) and 12/35 (43.2%) cases associated to the grade of the tumors (p = 0.019, p = 0.001, respectively) and to the survival rate of the patients (p = 0.037, p = 0.001, respectively). EGFR overall expression was also correlated to the gene copies (p = 0.020). EGFR gene numerical alterations –although rare– and also chromosome 7 aneuploidy maybe affect prognosis in HCC patients. To our knowledge this is the first chromogenic in situ hybridization analysis based on tissue microarrays in hepatocellular carcinoma.

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Acknowledgments

The authors declare no conflicts of interest. The authors are also very grateful to Mr G Vilaras and Mrs P Tzoumakari, Technologists in the Departments of Pathology, Medical School, University of Athens and 417 VA Hospital (NIMTS), Athens, Greece, respectively for the quality of their laboratorial work.

This paper was granted by Hellenic Society for the Study of the Liver (2007–2008 Grant Program).

Conflict of interest statement

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Dept of Molecular Cytopathology, 417 NIMTS Hospital, Athens, Greece

    Evangelos Tsiambas

  2. Dept of Surgery, Bioclinic, Athens, Greece

    Loukas Manaios

  3. Dept of Internal Medicine, 401 GA Hospital, Athens, Greece

    Costas Papanikolopoulos & Dimitrios N. Rigopoulos

  4. Dept of Gastroenterology, 251 AF Hospital, Athens, Greece

    Dimitrios Tsounis

  5. Dept of Pathology, 417 VA Hospital, Athens, Greece

    Andreas Karameris & Christos Kravvaritis

  6. Dept of Gastroenterology, Hippokration H, Medical School, University of Athens, Athens, Greece

    Aspasia Soultati & Spyridon Dourakis

  7. Dept of Pathology, Medical School, National & Kapodistrian University of Athens, Athens, Greece

    Theodoros Sergentanis & Efstratios Patsouris

  8. Dept of Thoracic Surgery, Evangelismos Hospital, Athens, Greece

    Antigoni Koliopoulou

  9. Dept of Molecular Cytopathology, 417 NIMTS Hospital, Patriarchou Grigoriou E 17, Ag Paraskevi Attiki, 15341, Greece

    Evangelos Tsiambas

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  1. Evangelos Tsiambas
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  2. Loukas Manaios
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  11. Efstratios Patsouris
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Correspondence to Evangelos Tsiambas.

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Tsiambas, E., Manaios, L., Papanikolopoulos, C. et al. Chromogenic In Situ Hybridization Analysis of Epidermal Growth Factor Receptor Gene/Chromosome 7 Numerical Aberrations in Hepatocellular Carcinoma Based on Tissue Microarrays. Pathol. Oncol. Res. 15, 511–520 (2009). https://doi.org/10.1007/s12253-008-9146-5

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  • DOI: https://doi.org/10.1007/s12253-008-9146-5

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