|
|
Molecular genetic characteristics of salivary gland tumors in differential diagnosis and prognosis prediction
Hauer, Lukáš ; Skálová, Alena (advisor) ; Laco, Jan (referee) ; Mazánek, Jiří (referee)
Molecular genetic characteristics of salivary gland tumors in differential diagnosis and prognosis prediction Abstract: In the presented manuscript the author summarizes the current knowledge on molecular biomarkers of salivary gland cancer, focusing on tumor-type specific fusion oncogenes and their use as diagnostic, prognostic and therapeutic biomarkers. In detail, the author deals with adenoid cystic carcinoma (AdCC), the second most common salivary gland cancer. New facts of its biological behavior as well as new fusion oncogenes probably responsible for its carcinogenesis were described in the last few years. A retrospective case series evaluating 27 patients suffering from AdCC, who were treated at the University Hospital in Pilsen in the last 30 years (1986- 2016), is presented in this study. The following characteristics were observed: age, gender, tumor location, clinical stage at diagnosis, presence of regional and distant metastases, tumor grade, duration of follow-up, treatment and outcomes. Detection of the 1p36 deletion and the t(6;9)(q22-23;p23-24) chromosomal translocation resulting in the MYB-NFIB gene fusion were performed. The incidence of AdCC in minor salivary glands, submandibular gland, parotid gland and sublingual gland was 41 %, 26 %, 22 % and 11% respectively. The following staging...
|
|
|
Correlation of Molecular-Genetic and Morphological Markers of Rare Salivary Gland Tumors
Šteiner, Petr ; Skálová, Alena (advisor) ; Laco, Jan (referee) ; Šíma, Radek (referee)
Thesis deals with relationship between histomorphological and molecular-genetic findings of selected salivary gland tumors. Author, as a molecular-cytogeneticist mainly focused on detection of tumor-specific translocations of the salivary gland tumors which can serve as differential diagnostic markers. The thesis is composed as a commented files of authors own publications, and it is divided into four parts. First part deepens the knowledge of salivary adenoid cystic carcinoma. It was proved, that t(6;9)(q22-23;p23-24) resulting in fusion of transcription factors MYB-NFIB, or more rarely t(8;9) resulting in MYBL1-NFIB fusion represent robust differential diagnostic marker of adenoid cystic carcinoma. Further it was proved, that the 1p36 deletion can serve as an unfavorable prognostic indicator of adenoid cystic carcinoma, as the patients with 1p36 deletion had significantly lower survival. Second part summarizes new developments about mammary analogue secretory carcinoma (MASC), which was described by our group as a new salivary tumor entity characterized by translocation t(12;15)(p13;q25) resulting in ETV6-NTRK3 fusion. Another novel observation is a discovery of ETV6-RET fusion in a subset of MASC cases. Further, the first two MASCs of nasal mucosa origin have been described. Third part consists...
|
|
|
Immunoprofiling in patients with HPV-associated and non-associated head and neck squamous cell carcinoma
Lukešová, Eva ; Klozar, Jan (advisor) ; Šlapák, Ivo (referee) ; Laco, Jan (referee)
Head and neck squamous cell carcinomas (HNSCC) remain a significant cause of morbidity worldwide, with approximately 550,000 new cases diagnosed each year. The main etiological factors include smoking and alcohol consumption. The incidence of non-oropharyngeal HNSCC is gradually decreasing while the incidence of squamous cell oropharyngeal carcinoma (OPSCC) is still on the rise. This increasing incidence can be most likely attributed to an increasing prevalence of human papillomavirus (HPV) infection. From the clinical point of view the most significant fact is that patients with HPV positive OPSCC have better prognosis. HNSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. Therefore, we focused on the research of the immunological profile of patients with HNSCC of viral and non-viral etiology. In our study, 110 patients with HNSCC were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA detected in the tumor tissue. Basic lymphocyte subpopulations (CD3+, CD4+ CD25+ Treg, CD4+ CD25+ FoxP3 Treg, CD4+, CD8+, CD19, and CD3- CD16+ CD56+ cells) were determined by flow cytometry in the peripheral blood (PB). We observed...
|
|
|
Immunohistochemical and Molecular Genetic Methods in the Head and Neck Pathology
Baněčková, Martina ; Skálová, Alena (advisor) ; Stárek, Ivo (referee) ; Laco, Jan (referee)
Current doctoral thesis is dealing with morphology, immunohistochemistry, molecular genetics and biological behavior of head and neck tumors with a particular emphasis on salivary gland and sinonasal lesions. Dr. Martina Baneckova has focused on this topic during her postgraduate studies at Charles University, Medical Faculty in Pilsen, in the years 2017 - 2020. In her publication activity, the author focused on rare tumors of the head and neck. A total of 9 publications were published over a span of three years are presented in a form of a commentary. Four of them are first-author papers and these are introduced briefly below. The first study entitled "Mammary analog secretory carcinoma of the nasal cavity: Characterization of 2 cases and their distinction from other low-grade sinonasal adenocarcinomas" deals with the relationship of newly described entities, secretory carcinoma (SC) of the nasal cavity and ETV6-rearranged low-grade sinonasal adenocarcinoma (LG SNAC). It is important to distinguish these 2 entities because of different clinical behaviors. Low-grade non-ITAC, including ETV6-rearranged LG SNAC mostly behave in an indolent manner, whereas SC is a malignancy with metastatic potential. It is important to be aware of the possible occurrence of SC in the sinonasal region, as in this area...
|
|
|
Serrated Lesions of Gastrointestinal Tract and Significance of Serrated Changes in Mucosa of Inflammatory Bowel Disease Patients
Kamarádová, Kateřina ; Laco, Jan (advisor) ; Hermanová, Markéta (referee) ; Ehrmann, Jiří (referee)
Patients with inflammatory bowel disease (IBD) have an elevated risk of developing colorectal carcinoma (CRC). IBD-dysplasia is regarded as a conventional precursor for IBD- associated carcinoma. (1-2) Other types of non-conventional mucosal changes with serrated and villous hypermucinous morphology have also been reported but their preneoplastic potential is still not well elucidated. (3-4) The aim of the study was to retrospectively review samples from IBD patients focusing on detection of mucosal lesions including non-conventional lesions and evaluate their relationship and immunohistochemical and molecular properties. Surgical specimens and/or endoscopical biopsy samples of IBD patients examined during a 10-year period were reviewed. Mucosal lesions were divided into three groups - group 1 of non-conventional lesions, group 2 of true serrated polyps, and group 3 of IBD-dysplasia and colorectal carcinoma. Detailed morphological evaluation, immunohistochemical analysis of mismatch repair proteins and/or MLH1, p53 and O6 -methylguanine DNA methyltransferase (MGMT) expression, and molecular analysis for KRAS, NRAS and BRAF gene mutation was performed in all lesions. Overall, samples from 309 IBD patients were reviewed. A total of 88 mucosal lesions were found in 51 patients. Most common were lesions...
|
|
|
Correlation of Immunohistochemical and Molecular Methods in Diagnostics of Salivary Gland Tumors
Horáková, Markéta ; Skálová, Alena (advisor) ; Laco, Jan (referee) ; Dušková, Jaroslava (referee)
This doctoral thesis is dealing with the correlation of morphological, immunohistochemical and genetical findings in malignant tumors of salivary glands. The first half of the thesis comprises the summary of current knowledge about salivary malignancies. The second half is presenting the research itself. The research results are divided into three parts. The first part is presenting the method of "2-step diagnostic test" of malignant tumors. This screening test aims to find new, so far not described gene aberrations with a focus on malignant tumors of salivary glands. This method takes place in two consecutive steps. In the first step the material is examined by an immunohistochemical mixture of antibodies, which non-specifically detects aberration in the genes NTRK1-3, ALK and ROS1. In the second step all positive cases are subjected to highly sensitive and specific molecular-genetic examination by the method of next generation sequencing (NGS) using the Archer kit. In the second part of the work there has been designed the approach to the cytological diagnosis of salivary secretory carcinoma by the fine-needle aspiration (FNA). This part is describing to the details the cytomorphology of secretory carcinoma in both, Pap smears and cell blocks, from which additional immunocytochemical and genetic...
|
|
|
Correlation of Molecular-Genetic and Morphological Markers of Rare Salivary Gland Tumors
Šteiner, Petr ; Skálová, Alena (advisor) ; Laco, Jan (referee) ; Šíma, Radek (referee)
Thesis deals with relationship between histomorphological and molecular-genetic findings of selected salivary gland tumors. Author, as a molecular-cytogeneticist mainly focused on detection of tumor-specific translocations of the salivary gland tumors which can serve as differential diagnostic markers. The thesis is composed as a commented files of authors own publications, and it is divided into four parts. First part deepens the knowledge of salivary adenoid cystic carcinoma. It was proved, that t(6;9)(q22-23;p23-24) resulting in fusion of transcription factors MYB-NFIB, or more rarely t(8;9) resulting in MYBL1-NFIB fusion represent robust differential diagnostic marker of adenoid cystic carcinoma. Further it was proved, that the 1p36 deletion can serve as an unfavorable prognostic indicator of adenoid cystic carcinoma, as the patients with 1p36 deletion had significantly lower survival. Second part summarizes new developments about mammary analogue secretory carcinoma (MASC), which was described by our group as a new salivary tumor entity characterized by translocation t(12;15)(p13;q25) resulting in ETV6-NTRK3 fusion. Another novel observation is a discovery of ETV6-RET fusion in a subset of MASC cases. Further, the first two MASCs of nasal mucosa origin have been described. Third part consists...
|
|
|
Molecular genetic characteristics of salivary gland tumors in differential diagnosis and prognosis prediction
Hauer, Lukáš ; Skálová, Alena (advisor) ; Laco, Jan (referee) ; Mazánek, Jiří (referee)
Molecular genetic characteristics of salivary gland tumors in differential diagnosis and prognosis prediction Abstract: In the presented manuscript the author summarizes the current knowledge on molecular biomarkers of salivary gland cancer, focusing on tumor-type specific fusion oncogenes and their use as diagnostic, prognostic and therapeutic biomarkers. In detail, the author deals with adenoid cystic carcinoma (AdCC), the second most common salivary gland cancer. New facts of its biological behavior as well as new fusion oncogenes probably responsible for its carcinogenesis were described in the last few years. A retrospective case series evaluating 27 patients suffering from AdCC, who were treated at the University Hospital in Pilsen in the last 30 years (1986- 2016), is presented in this study. The following characteristics were observed: age, gender, tumor location, clinical stage at diagnosis, presence of regional and distant metastases, tumor grade, duration of follow-up, treatment and outcomes. Detection of the 1p36 deletion and the t(6;9)(q22-23;p23-24) chromosomal translocation resulting in the MYB-NFIB gene fusion were performed. The incidence of AdCC in minor salivary glands, submandibular gland, parotid gland and sublingual gland was 41 %, 26 %, 22 % and 11% respectively. The following staging...
|
|
|
Immunoprofiling in patients with HPV-associated and non-associated head and neck squamous cell carcinoma
Lukešová, Eva ; Klozar, Jan (advisor) ; Šlapák, Ivo (referee) ; Laco, Jan (referee)
Head and neck squamous cell carcinomas (HNSCC) remain a significant cause of morbidity worldwide, with approximately 550,000 new cases diagnosed each year. The main etiological factors include smoking and alcohol consumption. The incidence of non-oropharyngeal HNSCC is gradually decreasing while the incidence of squamous cell oropharyngeal carcinoma (OPSCC) is still on the rise. This increasing incidence can be most likely attributed to an increasing prevalence of human papillomavirus (HPV) infection. From the clinical point of view the most significant fact is that patients with HPV positive OPSCC have better prognosis. HNSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. Therefore, we focused on the research of the immunological profile of patients with HNSCC of viral and non-viral etiology. In our study, 110 patients with HNSCC were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA detected in the tumor tissue. Basic lymphocyte subpopulations (CD3+, CD4+ CD25+ Treg, CD4+ CD25+ FoxP3 Treg, CD4+, CD8+, CD19, and CD3- CD16+ CD56+ cells) were determined by flow cytometry in the peripheral blood (PB). We observed...
|
|
|
Detection of circulating antibodies to determination of autoimmuno diseases by means of immunofluorescence.
Sieglová, Kateřina ; Nachtigal, Petr (advisor) ; Laco, Jan (referee)
Kateřina Sieglová Detection of circulating antibodies to determination of autoimmuno diseases by means of imunofluorescence. Bachelor thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Medical Laboratory Technician Background: The aim of this thesis is to explore of coherence between the presence of antibody against anti brush border antibody (ABBA) and idiopatic bowel disease (Crohn's disease and ulcerative colitis). Methods: Evidence of connection idiopatic bowel disease with positive ABBA test is examine by two perspectives, which are used for selecting and comparising of data. The first way is comparison of the number ABBA positive patients with their diagnosis of endoscopic biopsy. The second way check the positivity or negativity of ABBA examination of all patients with diagnose of idiopatic bowel disease. Experimental part summarize by this way the results, which was done at the Fingerland institute of pathology since 2009 to 2011. Results: The survey showed that among all the ABBA-positive patients is a large group of those who don't have the morphological signs of Inflammatory Bowel Disease - 72,47%. 66.67% of patients with a clinical diagnosis of Crohn's disease, and 39.37% of patients with ulcerative colitis are ABBA positive. Conclusion: The results shows, that...
|
guest ::
