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Histopathology and Molecular Biology of Gastrointestinal Tumours
Červenková, Lenka ; Souček, Pavel (advisor) ; Eckschlager, Tomáš (referee) ; Pivovarčíková, Kristýna (referee)
The incidence and mortality of gastrointestinal cancers are at a level that represents a serious problem. These tumours have non-specific clinical symptoms, which often results in late diagnosis. In recent years, there have been significant advances in the identification and monitoring of molecular markers of tumour changes in the diagnosis, prognosis and treatment of these diseases. However, clinical oncology still faces a shortage of such biomarkers. The aim of this study was to find new biomarkers that correlate especially with prognostic indicators and predictors of treatment response or chemoresistance in gastrointestinal tract cancers. This thesis is based on 5 studies addressing ductal adenocarcinoma of the pancreas, colorectal cancer and hepatocellular carcinoma using IHC and molecular methods. All studies were performed using archival formalin-fixed paraffin-embedded samples. The main results include immunohistochemical evidence of protein expression of MRP2, SLC22A3 and SUR1/ABCC8 transporters and its significant association with the prognosis of pancreatic adenocarcinoma. Patients without SLC22A3 protein expression in the apical membrane were found to have significantly shorter disease-free and overall survival. We found longer disease-free survival in patients with positive membrane...
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Clinicopathological, Morphological, Immunohistochemical, and Molecular Biological Features of Tumors of Genitourinary Tract
Rogala, Joanna Dominika ; Pivovarčíková, Kristýna (advisor) ; Pitra, Tomáš (referee) ; Rychlý, Boris (referee)
The thesis "Clinicopathological, morphological, immunohistochemical and molecular biological features of tumours of genitourinary tract" includes seven commented articles from the area of genitourinary (GU) tract neoplasms. Due to the wide spectrum of tumours of the GU tract, the presented dissertation is limited only to morphologic, immunohistochemical and molecular aspects of renal tumours - in the field of pathology, we have observed fundamental changes in recent years and where molecular techniques have begun to play an integral role in pathological examination. The introduction comments current 5th edition of WHO classification of kidney tumours, it emphasizes changes and new entities defined by distinctive morphology and molecular signature as well as comments on new insights in well-established entities. In the results, there are presented recently published original publications describing variant morphologies of common tumours with their immunohistochemical and molecular profile, as well as newly describe entity with its immunohistochemical and molecular characteristics. In the conclusion, dynamics of changes in renal tumours classification is discussed together with the importance of molecular testing, its therapeutic implications and limitations.
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Chromophobe Renal Cell Cancer
Kolář, Jiří ; Hora, Milan (advisor) ; Pivovarčíková, Kristýna (referee) ; Fedorko, Michal (referee)
Introduction: Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of RCC after clear cell RCC and papillary RCC. It is a relatively indolent subtype of RCC with approximately 5% risk of progression and development of metastases after surgical treatment. Predicting the clinical behaviour of chRCC by histologic features has so far proven to be challenging which is related to the lack of a validated grading system for this type of renal cancer. Historically, several grading schemes were proposed specifically for chRCC. However, none of them has proven useful in clinical practice. Two main histological subtypes of chRCC are known, namely classic and eosinophilic. Moreover, several aberrant histologic subtypes have been described, including adenomatoid microcystic pigmented, multicystic, neuroendocrine, papillary, oncocytic and small cell-like. It has been previously reported that both main subtypes of chRCC (classic and eosinophilic) have no differences in their prognosis. It is hypothesized that also these rare histological subtypes are not associated with differences in clinical outcomes. Nevertheless, this hypothesis has never been tested or confirmed by clinical data. Materials and methods: The aim of this thesis was to assess the impact of histologic diversity in chRCC...
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Tumors of Urogenital Tract, Molecular Genetic Characteristics and Impact on Biological Behavior
Pivovarčíková, Kristýna ; Hes, Ondřej (advisor) ; Mandys, Václav (referee) ; Vernerová, Zdeňka (referee)
The Ph.D. thesis is a collection of seven commented articles on the topic of molecular-genetic of urogenital tumors. The spectrum of urogenital lesions is very wide, there is lots of new insights in field of urogenital pathology. Therefore, presented Ph.D. thesis is focused only on small part of urogenital neoplasms - renal cell carcinomas characterized by papillary growing pattern. The introduction presents different entities with papillary morphology, there are specified basic morphological, immunohistochemical and molecular-genetic characteristic of these lesions, their differential diagnosis is commented. In the results, there are presented recently published studies dealing with newly described entities of renal neoplasias, heterogenity of molecular genetic studies in individual tumorous groups is established, prognostic significance is commented, typical pitfalls are introduced. In the conclusions, the limitations of the use molecular-genetic methods are discussed and clinical outcome and significance is evaluated.
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Tumors of Urogenital Tract, Molecular Genetic Characteristics and Impact on Biological Behavior
Pivovarčíková, Kristýna ; Hes, Ondřej (advisor) ; Mandys, Václav (referee) ; Vernerová, Zdeňka (referee)
The Ph.D. thesis is a collection of seven commented articles on the topic of molecular-genetic of urogenital tumors. The spectrum of urogenital lesions is very wide, there is lots of new insights in field of urogenital pathology. Therefore, presented Ph.D. thesis is focused only on small part of urogenital neoplasms - renal cell carcinomas characterized by papillary growing pattern. The introduction presents different entities with papillary morphology, there are specified basic morphological, immunohistochemical and molecular-genetic characteristic of these lesions, their differential diagnosis is commented. In the results, there are presented recently published studies dealing with newly described entities of renal neoplasias, heterogenity of molecular genetic studies in individual tumorous groups is established, prognostic significance is commented, typical pitfalls are introduced. In the conclusions, the limitations of the use molecular-genetic methods are discussed and clinical outcome and significance is evaluated.
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