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Immunological features of esophageal carcinoma in prognosis and therapy
Šnajdauf, Martin ; Lischke, Robert (advisor) ; Vrba, Radek (referee) ; Stříž, Ilja (referee)
Esophageal cancer belongs to the gastrointestinal malignancies with the worst prognosis. Current treatment options, including surgical resection, chemotherapy, radiotherapy, or a combination of these methods, have low efficacy and the five-year survival rate for patients with esophageal cancer is approximately 10 to 15 %. In the last decade, immunotherapy has become the leading treatment modality for metastatic tumors. However, the success of immunotherapeutic approaches does not only depend on the infiltration of the tumor microenvironment with immune cells but also on the phenotype of these infiltrating cells. The aim of this project was to evaluatethe immunological features of tumor-infiltrating lymphocytes obtained from different tissue compartments (tumor, peritumoral tissue, adjacent healthy tissue, and lymph node) of patients during surgical resection and to compare them with clinical and histopathological data of patients. We observed that the distribution of NK (natural killer) cells, CD8 and CD4 positive T cells was different in each tissue compartment. While the lymph nodes had the highest percentage of T cells, the opposite was seen in NK cells. The proportion of NK cells was the lowest in the lymph nodes. The expression of death receptors FasR and DR3 (death receptor 3) was the lowest...
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Immunohistochemical and molecular-genetic markers in predicting the progression of esophageal neoplasia in correlation with pathophysiology
Kollár, Marek ; Martínek, Jan (advisor) ; Suchánek, Štěpán (referee) ; Mandys, Václav (referee)
Introduction: Esophageal cancer ranks eighth among the most common malignancies worldwide. The two most common types are adenocarcinoma and spinocellular carcinoma. Correct histopathological diagnosis, cancer staging and identification of predictive risk factors of progression are important in terms of further disease course and management. While patients with mucosal carcinoma without risk factors are treated endoscopically, those with submucosal invasion or mucosal carcinoma with risk factors are referred for surgical therapy according to current recommendations. Histopathology is still considered the gold standard in diagnosis, often used in conjunction with immunohistochemistry, e.g., to document a TP53 gene mutation, which plays an important role in the pathogenesis and progression of esophageal dysplasia. New diagnostic methods, such as confocal laser endomicroscopy (CLE), also play an important role. Other crucial factors include patient follow-up, early and reliable detection of persistent or recurrent lesions. Aims, methods and patients: In the thesis, 4 separate, partly connected projects are assessed together, with a partial overlap of patients. The aims of the individual projects were as follows: 1) To identify predictive factors of esophageal cancer progression, risk of metastasis and...
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