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Uncommon tumors of urogenital tract, their biological behaviour, morphology and cytogenetics
Michalová, Květoslava ; Hes, Ondřej (advisor) ; Dundr, Pavel (referee) ; Křen, Leoš (referee)
Current doctoral thesis is dealing with biological behavior, morphology and cytogenetical features of rare urogenital tumors with a particular emphasis on renal tumors. Dr. Kvetoslava Michalova (birth name Peckova) was focused on this topic during her postgradual study at Charles University in Prague, Medical Faculty in Pilsen, in years 2014-2017. In her publication activity, the author focused on rare tumors of urogenital tract. The 20 publications published over a span of three years are presented in a form of a commentary. Seven of them are first-author papers and these are briefly introduced below. The first paper entitled "Renal cell carcinoma with leiomyomatous stroma- further immunohistochemical and molecular genetic characteristics of unusual entity" dealt with the relationship between renal cell carcinoma (RCC) with leiomyomatous stroma (LS) and clear cell RCC with reactive LS. It led to the conclusion, that only genetic analysis of VHL gene mutation, VHL hypermatylation and chromosome 3p loss of heterozygosity can be used as a distinguishing tool. The "real" RCC with LS lack the above described genetic abnormalities which is in contrary to the clear cell RCC, which is characterized by them. The distinction between these two entities is of clinical importance, as the "real" RCC with LS...
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Nodal and Extranodal Lymphomas: Clinicopathological, Immunohistochemical, Molecular-Biological Charactersistics
Veselá, Pavla ; Boudová, Ludmila (advisor) ; Křížková, Věra (referee) ; Křen, Leoš (referee)
3 Abstract The doctor thesis is composed of two major studies, both of them focused on the mantle cell lymphoma (MCL). The first part deals with the verification of the prognostic influence of Mantle Cell Lymphoma International Prognostic Index (MIPI) and of the proliferative activity in 235 patients with MCL diagnosed in 1996-2008 in the Czech Republic. This population study was performed in the collaboration with the Czech Lymphoma Study Group. The clinical data of patients were completed in April 2012. The diagnosis of MCL was confirmed by our central histopathologic examination of pretherapeutic histological samples. The median overall survival (OS) was 47 months, median progression free survival (PFS) was 22 months. We demonstrated the influence of proliferative activity, MIPI and of the therapy type (intensive/non-intensive) on OS and PFS in univariate and multivariate analysis. Using univariate analysis we showed the prognostic influence of aggressive/other cytomorphological variants of MCL, nodal/extranodal localization of primary sample and also of the variants of MIPI - s-MIPI, MIPIb and a completely new variant of MIPI - combined MIPI. The prognostic influence of growth pattern and of the results of immunohistochemical reaction with CD23, CD5 and cyclin D1 antibodies were not confirmed. The other...
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Breast cancer biomarkers after neoadjuvant therapy.
Skálová, Helena ; Povýšil, Ctibor (advisor) ; Kolář, Zdeněk (referee) ; Křen, Leoš (referee)
Chemotherapy is one of the basic therapeutic procedures of breast cancer (BC) which may precede and/or follow the surgical resection of a tumor as a part of neoadjuvant or adjuvant therapy. However, the selective pressure of chemotherapy on tumor cells may change their molecular and expression profile and thus also their chemosensitivity. The aim of our work was to document the expression changes of selected markers in BC after neoadjuvant chemotherapy, which may contribute to the understanding of the role of these proteins and genes in tumor response to chemotherapy and the development of chemoresistance. Immunohistochemical analysis of expression of standard BC markers [estrogen (ER) and progesterone receptors (PR), HER2 and proliferation activity (Ki67)] and intercellular junction proteins (claudin 1, 3 and 4, E- and N-cadherin) before and after neoadjuvant chemotherapy revealed a decrease of PR, Ki67 and claudin 3 expression and an increase of claudin 1 expression. The expression of ER, HER2, claudin 4, E- and N-cadherin proved to be stable. Assessment of standard BC markers is performed routinely during a bioptic investigation as a necessary factor for therapy indication. Our results support the current recommendations for the re-examination before indication of adjuvant chemotherapy. Claudins...
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Uncommon tumors of urogenital tract, their biological behaviour, morphology and cytogenetics
Michalová, Květoslava ; Hes, Ondřej (advisor) ; Dundr, Pavel (referee) ; Křen, Leoš (referee)
Current doctoral thesis is dealing with biological behavior, morphology and cytogenetical features of rare urogenital tumors with a particular emphasis on renal tumors. Dr. Kvetoslava Michalova (birth name Peckova) was focused on this topic during her postgradual study at Charles University in Prague, Medical Faculty in Pilsen, in years 2014-2017. In her publication activity, the author focused on rare tumors of urogenital tract. The 20 publications published over a span of three years are presented in a form of a commentary. Seven of them are first-author papers and these are briefly introduced below. The first paper entitled "Renal cell carcinoma with leiomyomatous stroma- further immunohistochemical and molecular genetic characteristics of unusual entity" dealt with the relationship between renal cell carcinoma (RCC) with leiomyomatous stroma (LS) and clear cell RCC with reactive LS. It led to the conclusion, that only genetic analysis of VHL gene mutation, VHL hypermatylation and chromosome 3p loss of heterozygosity can be used as a distinguishing tool. The "real" RCC with LS lack the above described genetic abnormalities which is in contrary to the clear cell RCC, which is characterized by them. The distinction between these two entities is of clinical importance, as the "real" RCC with LS...
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Nodal and Extranodal Lymphomas: Clinicopathological, Immunohistochemical, Molecular-Biological Charactersistics
Veselá, Pavla ; Boudová, Ludmila (advisor) ; Křížková, Věra (referee) ; Křen, Leoš (referee)
3 Abstract The doctor thesis is composed of two major studies, both of them focused on the mantle cell lymphoma (MCL). The first part deals with the verification of the prognostic influence of Mantle Cell Lymphoma International Prognostic Index (MIPI) and of the proliferative activity in 235 patients with MCL diagnosed in 1996-2008 in the Czech Republic. This population study was performed in the collaboration with the Czech Lymphoma Study Group. The clinical data of patients were completed in April 2012. The diagnosis of MCL was confirmed by our central histopathologic examination of pretherapeutic histological samples. The median overall survival (OS) was 47 months, median progression free survival (PFS) was 22 months. We demonstrated the influence of proliferative activity, MIPI and of the therapy type (intensive/non-intensive) on OS and PFS in univariate and multivariate analysis. Using univariate analysis we showed the prognostic influence of aggressive/other cytomorphological variants of MCL, nodal/extranodal localization of primary sample and also of the variants of MIPI - s-MIPI, MIPIb and a completely new variant of MIPI - combined MIPI. The prognostic influence of growth pattern and of the results of immunohistochemical reaction with CD23, CD5 and cyclin D1 antibodies were not confirmed. The other...
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