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Molecular biological detection of viral and bacterial pathogens and their relationship
Kašpírková, Jana ; Hes, Ondřej (advisor) ; Daum, Ondřej (referee) ; Boudová, Ludmila (referee) ; Putzová, Martina (referee)
1 We report a case of an eccrine syringofibroadenoma (ESFA) associated with well- differentiated squamous cell carcinoma. The patient was an 85-year-old man, who had a 2.5x2.5-cm, brown-colored ulcerated nodule, with a fragile, flesh-colored bleeding surface located beyond the metacarpophalangeal joint of the second finger of his left hand. Histopathologically, there were areas of a well-differentiated squamous cell carcinoma, alternating with the typical area of ESFA characterized by anastomosing cords, strands, and columns of epithelial cells extending from the crusted epidermis into a thickened, edematous, myxoid vascular-rich dermis. Immunohistochemically, the areas with dysplastic epithelium were positive for p16, whereas the benign ESFA parts tested negative. Human papillomavirus was detected in the lesional tissue by polymerase chain reaction, and the subsequent sequencing analysis demonstrated that the virus was close to human papillomavirus type 107. 2 The authors report a case of basaloid carcinoma involving the anus and rectum of a 57-year- old woman. Microscopically, the tumor showed unusual morphologic features strongly resembling a spiradenocylindroma because it consisted, in most parts, of basaloid cell nodules arranged in a jigsaw-puzzle fashion containing or surrounded by eosinophilic basal...
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Immunopathological and immunogenetic aspects of haematopietic stem cell and solid organ transplantations
Jindra, Pavel ; Boudová, Ludmila (advisor) ; Fakan, František (referee) ; Slavčev, Antonij (referee)
The genetic diversity of KIR genes and genotypes resembles of the HLA. Although the genes encoding KIR and HLA are located in different chromosomes and segregate independently, there is some evidence of some kind of co-evolution. Therefore, one could expect reduced KIR diversity within the HLA restricted population. A total of 41 unrelated individuals homozygous for ancestral HLA haplotype AH8.1 (HLA-A*0101-Cw*0701-B*0801- DRB1*0301-DQB1*0201), were typed for KIR genes. Over all, fourteen different genotypes were identified. The observed frequencies of KIR genes and genotypes composition generally mirror the published frequencies in Caucasians. Non-framework genes with frequency of more than 90 % included KIR2DL1, KIR2DL3, KIR3DL1, KIR2DS4 and KIR2DP1. Except for the KIR2DS4, all activating genes presented frequencies bellow 50 %. KIR2DS5 was the least frequent among activating genes (17 %), whereas KIR2DL5 (37 %) among inhibitory ones. The most frequent (39 %) was AA genotype. 22 individuals (54 %) had a copy of KIR haplotype A and B (AB genotype), whereas 3 (7%) were homozygous for B (BB genotype). Nine of 14 reported genotypes occurred only in one individual. Comparing with published and recorded genotypes (www.allelefrequencies.net), 5 genotypes were reported in less than 20 individuals worldwide and...
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Correlation of morphologic and moleculargenetic features of selected tumors
Šíma, Radek ; Skálová, Alena (advisor) ; Boudová, Ludmila (referee) ; Ehrmann, Jiří (referee)
We present a series of 16 salivary gland tumors with histomorphological and immunohistochemical features reminiscent of secretory carcinoma of the breast. This is a hitherto undescribed and distinctive salivary gland neoplasm, with features resembling both salivary acinic cell carcinoma and low grade cystadenocarcinoma, as well as displaying strong similarities to breast secretory carcinoma. Microscopically, the tumors have a lobulated growth pattern and are composed of microcystic and glandular spaces with abundant eosinophilic homogenous or bubbly secretory material positive for PAS, mucicarmine, MUC1, MUC4 and mammaglobin. The neoplasms also show strong vimentin, S-100 protein, and STAT5a positivity. For this tumor we propose a designation mammary analogue secretory carcinoma of salivary glands (MASC). The 16 patients comprised 9 men and 7 women, with a mean age of 46 years (range 21-75). Thirteen cases occurred in the parotid gland, and one each in the minor salivary glands of the buccal mucosa, upper lip, and palate. The mean size of the tumors was 2.1 cm (range 0.7 to 5.5 cm). The duration of symptoms was recorded in 11 cases and ranged from 2 months to 30 years. Clinical follow-up was available in 13 cases, and ranged...
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The Role of Antiangiogenic Therapy in Mantle Cell Lymphoma
Kovaříková, Petra ; Klener, Pavel (advisor) ; Kalinová, Markéta (referee) ; Boudová, Ludmila (referee)
Mantle cell lymphoma (MCL) is a subtype of B-non-Hodgkin's lymphoma, characterized by often relapses. Despite an Ibrutinib (a Bruton's kinase inhibitor) implementation into salvage therapy, these patients often relapse with biologically highly aggressive disease and very poor prognosis. An increased activation of alternative metabolic pathways was described as one of ibrutinib-resistance mechanisms. Some of these pathways have also significant proangiogenic activity (e.g. PI3K-AKT-mTOR). In presented study, we established and standardized a real-time ultrasound and photoacoustic imaging of neovascularization and tissue oxygenation of subcutaneous MCL tumors in mice. Ultrasound and photoacoustic imaging is a fast, non-invasive method for angiogenesis evaluation in subcutaneous tumors with huge preclinical potential. Using MCL mice models, we also demonstrated the importance of CD31/PECAM-1 expression for engraftment, growth and spread of MCL cells in vivo. The level of CD31 expression in primary MCL cell (obtained directly from MCL patients) positively correlates with extent of extranodal involvement. CD31 facilitates survival and regulates extranodal spread of mantle cell lymphoma. We found that increased VEGFA expression causes not only increased microvessel density due to higher sprouting...
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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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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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Molecular biological detection of viral and bacterial pathogens and their relationship
Kašpírková, Jana ; Hes, Ondřej (advisor) ; Daum, Ondřej (referee) ; Boudová, Ludmila (referee) ; Putzová, Martina (referee)
1 We report a case of an eccrine syringofibroadenoma (ESFA) associated with well- differentiated squamous cell carcinoma. The patient was an 85-year-old man, who had a 2.5x2.5-cm, brown-colored ulcerated nodule, with a fragile, flesh-colored bleeding surface located beyond the metacarpophalangeal joint of the second finger of his left hand. Histopathologically, there were areas of a well-differentiated squamous cell carcinoma, alternating with the typical area of ESFA characterized by anastomosing cords, strands, and columns of epithelial cells extending from the crusted epidermis into a thickened, edematous, myxoid vascular-rich dermis. Immunohistochemically, the areas with dysplastic epithelium were positive for p16, whereas the benign ESFA parts tested negative. Human papillomavirus was detected in the lesional tissue by polymerase chain reaction, and the subsequent sequencing analysis demonstrated that the virus was close to human papillomavirus type 107. 2 The authors report a case of basaloid carcinoma involving the anus and rectum of a 57-year- old woman. Microscopically, the tumor showed unusual morphologic features strongly resembling a spiradenocylindroma because it consisted, in most parts, of basaloid cell nodules arranged in a jigsaw-puzzle fashion containing or surrounded by eosinophilic basal...
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Immunopathological and immunogenetic aspects of haematopietic stem cell and solid organ transplantations
Jindra, Pavel ; Boudová, Ludmila (advisor) ; Fakan, František (referee) ; Slavčev, Antonij (referee)
The genetic diversity of KIR genes and genotypes resembles of the HLA. Although the genes encoding KIR and HLA are located in different chromosomes and segregate independently, there is some evidence of some kind of co-evolution. Therefore, one could expect reduced KIR diversity within the HLA restricted population. A total of 41 unrelated individuals homozygous for ancestral HLA haplotype AH8.1 (HLA-A*0101-Cw*0701-B*0801- DRB1*0301-DQB1*0201), were typed for KIR genes. Over all, fourteen different genotypes were identified. The observed frequencies of KIR genes and genotypes composition generally mirror the published frequencies in Caucasians. Non-framework genes with frequency of more than 90 % included KIR2DL1, KIR2DL3, KIR3DL1, KIR2DS4 and KIR2DP1. Except for the KIR2DS4, all activating genes presented frequencies bellow 50 %. KIR2DS5 was the least frequent among activating genes (17 %), whereas KIR2DL5 (37 %) among inhibitory ones. The most frequent (39 %) was AA genotype. 22 individuals (54 %) had a copy of KIR haplotype A and B (AB genotype), whereas 3 (7%) were homozygous for B (BB genotype). Nine of 14 reported genotypes occurred only in one individual. Comparing with published and recorded genotypes (www.allelefrequencies.net), 5 genotypes were reported in less than 20 individuals worldwide and...
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Correlation of morphologic and moleculargenetic features of selected tumors
Šíma, Radek ; Skálová, Alena (advisor) ; Boudová, Ludmila (referee) ; Ehrmann, Jiří (referee)
We present a series of 16 salivary gland tumors with histomorphological and immunohistochemical features reminiscent of secretory carcinoma of the breast. This is a hitherto undescribed and distinctive salivary gland neoplasm, with features resembling both salivary acinic cell carcinoma and low grade cystadenocarcinoma, as well as displaying strong similarities to breast secretory carcinoma. Microscopically, the tumors have a lobulated growth pattern and are composed of microcystic and glandular spaces with abundant eosinophilic homogenous or bubbly secretory material positive for PAS, mucicarmine, MUC1, MUC4 and mammaglobin. The neoplasms also show strong vimentin, S-100 protein, and STAT5a positivity. For this tumor we propose a designation mammary analogue secretory carcinoma of salivary glands (MASC). The 16 patients comprised 9 men and 7 women, with a mean age of 46 years (range 21-75). Thirteen cases occurred in the parotid gland, and one each in the minor salivary glands of the buccal mucosa, upper lip, and palate. The mean size of the tumors was 2.1 cm (range 0.7 to 5.5 cm). The duration of symptoms was recorded in 11 cases and ranged from 2 months to 30 years. Clinical follow-up was available in 13 cases, and ranged...
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Clinical and pathologic correlation of complications of intensively treated hemato-oncological patients with a targeted focus to the involvement of the oral cavity and rare case of secondary neoplasia.
Vokurka, Samuel ; Boudová, Ludmila (advisor) ; Chlumská, Alena (referee) ; Faber, Edgar (referee)
Summary: In this thesis section "Oral Mucositis (OM) and oral Graft versus Host Disease (GVHD) in patients after allogeneic stem cells transplantation and with focus to FLU/MEL conditioning regimen" the author deals with following issues: 1. Literature overview: The overall negative impact of OM is mentioned and the complex pathogenesis, clinical characteristics, incidence and factors influencing both OM and GVHD are described. The histological features of GVHD and classification of it are mentioned, too. Conventional and reducedintensity conditioning transplant regimens, including FLU/MEL are presented. 2. Methodological section: Prospective observational study of 117 patients after allogeneic stem cells transplantation with BU/CY2/±ATG (26%), FLU/MEL (60%), FLU/CY (9%), Bu/FLU/ATG (2%) and HD-CY/ATG (2%) conditioning regimens. OM assed according to WHO criteria, GVHD assessed according to NIH criteria accepted by the EBMT. The statistical univariate analysis performed by means of GraphPad In Stat - Statistica Software (Man- Whitney, Fisher, t-test), p<0,05 considered significant. Multivariate analysis used in OM risk factors assessment. 3. Results: The OM incidence was significantly dependent on pre-transplant conditioning regimen (Bu/CY2/±ATG: 100%, FLU/MEL: 78%, FLU/CY: 9%, p=0,0001) in multivariable...
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