Fachbereich Veterinärmedizin



    Auswirkungen des histologischen Grades und des c-kit-Mutationsstatus auf das Proteinexpressionsprofil kaniner kutaner Mastzelltumoren (2013)

    Schlieben, Patricia (WE 12)
    Berlin: Mensch und Buch Verlag, 2013 — IX, 55 Seiten
    ISBN: 978-3-86387-333-2
    URL (Volltext): http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000094719
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    Tel.+49 30 838 62450 Fax.+49 30 838 62522

    Abstract / Zusammenfassung

    Cutaneous mast cell tumors (MCT) are one of the most common skin tumors in dogs. According to their histological appearance and the applied grading-system two or three different histological grades have to be distinguished. Grade 1 or low-grade MCT are characterized by well differentiated monomorphic tumor cells which neither tend to metastasize nor recur. Grade 3 or high-grade MCT are composed of dedifferentiated pleomorphic mast cells which often recur or even metastasize to distant organs. Although mast cell tumors are in the focus of research worldwide molecular details which provide the basis for this different clinical behavior are in most aspects unknown. Studies about KIT, the receptor for stem cell factor, and its proto-oncogene c-kit revealed promising results, as the identification of an activating internal tandem duplication in exon 11 lead to the assumption that KIT activity is of major relevance to MCT proliferation and progression. Impact of c-kit-mutations on the protein expression profile of mutated MCT cells is however unknown. Since recent studies identified c-kit-mutations in only 12 % of all MCT and 40 % of grade 3 MCT, other molecular alterations have to be responsible for the aggressive clinical behavior of grade 3 MCT.
    Therefore, the present study compared the protein expression patterns of grade 1 and grade 3 MCT (each n=5) and of MCT with or without c-kit-mutation (each n=3) by two-dimensional difference gel electrophoresis. Differentially expressed proteins were identified by mass spectrometry subsequently.
    Tumors of distinct histological grade differed in the expression of 13 proteins. Most of them are associated with stress resistance, cell motility and mast cell differentiation. Further studies are needed now to evaluate if these modified expressions patterns are responsible for the aggressive clinical behavior of grade 3 MCT.
    The comparison of c-kit-mutated and non-mutated MCT revealed 15 significantly differentially expressed proteins. Contrary to the second hypothesis no proteins with an association to increased proliferation activity were detectable. These results substantiate the assumption that activating mutations in the proto-oncogene c-kit are of less relevance for clinical behavior than the histological grade.