Klimuk B. Characterization of the mutational status of the Her-2/neu gene in breast cancer cells.

The dissertation was devoted for increasing the efficiency of determining the status of the Her-2/neu for patients with breast cancer by using fluorescent hybridization in situ (FISH), in combination with immunohistochemical (IHC) and molecular genetic data. When FISH evaluated tissue samples from women with breast cancer, according to the recommendations of the ASCO/CAP guidelines from 2007, 2013 and 2018, the percentage of cases without amplification of the Her-2/neu was the lowest using the recommendations from 2007. It has been shown that most cases with a positive mutation status of the Her-2/neu were detected using the 2013 ASCO/CAP recommendations. A significant number of cases with questionable results regarding the mutational status of the Her-2/neu were observed with the use of ASCO/CAP in 2018. The importance of additional work on case samples with questionable results to obtain a definitive determination of the mutational status of the Her-2/neu has been demonstrated. Sensitivity and specificity of FISH and IHC studies on breast tissue samples were determined in accordance with the recommendations of the ASCO/CAP guidelines 2007, 2013 and 2018. Polymorphic variants of the LSP1, TOX3 and FGFR2 have been identified, the presence of which potentially affects the mutation status of the Her-2/neu in breast cancer. Cases with the ratio (Her-2/neu)/CEP17 < 2 at the number of copies of the Her-2/neu per cell ≥ 6 in the conditions of unavailability of histological material of breast cancer for additional IHC study, as required by the guidelines of ASCO/CAP 2018 regarded as positive for the amplification status of the studied gene.