Neue immunhistochemische und molekulare Entwicklungen in der Hepatokarzinogenese

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Dokumentart: PhDThesis
Date: 2014-10
Language: English
Faculty: 4 Medizinische Fakultät
Department: Medizin
Advisor: Fend, F. (Prof. Dr.)
Day of Oral Examination: 2014-09-08
DDC Classifikation: 610 - Medicine and health
Keywords: Leber
Other Keywords: Primäre Leberkarzinome
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We report the immunohistochemical and molecular findings from a series of primary hepatic carcinomas, aiming for novel markers which may add to their diagnosis and gain more understanding of genetically altered genes and pathways implicated in their geneses. Regarding the standard immunostains applied, our findings are consistent with published literature and do strongly support the use of a panel of immune markers in the discrimination of primary liver malignancies. We also focused on the biological significance of an activated β-Catenin pathway (identified by Wnt1 immunoreactivity and the nuclear translocated β-Catenin) in hepatocarcinogenesis that can open the door to evaluate existing inhibitors of this pathway for future therapeutic management. It remains to be determined which genomic lesions identified by aberrant Wnt1 expression in these tumors are translated into nuclear β-Catenin accumulation. The study documented the expression of SALL4 as a stem cell marker in this series. Our findings suggest that SALL4 may play a role in recognizing the primary liver cancers, especially the poorly differentiated “primitive” cases. In addition SALL4 is one of the potential treatment targets in liver malignancies, especially that its expression is absent in the healthy adult liver. A unique type of expression of FGG immunostain was also observed in fibrolamellar carcinomas, the finding that supports the utility of FGG in FLC diagnosis, especially in the cases with less typical morphology or in discriminating FLC from scirrhous HCC. This review also identified BRAF-V600E gene mutations in HCC, FLC and HCC component of HCC/CCC but not in other CCC cases. This provides a potential path toward therapeutic intervention of the disease. We failed to identify a corresponding immunoreactivity with the commercially available BRAF antibody in the mutant cases. The conclusion is that the antibody is not a useful surrogate to detect BRAF-V600E mutations in primary liver malignancies. From a statistical point of view, this is a small-sample study, but we hope that we will contribute to a meta-analysis combining results of similar across studies of those immunohistochemical and molecular findings in an adequately sized study.

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