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Molecular characteristics of ductal carcinoma in situ, and their clinical impact
Böhm, Jan ; Zikán, Michal (advisor) ; Dundr, Pavel (referee) ; Strnad, Pavel (referee)
Objectives: Ductal carcinoma in situ (DCIS) is a non-invasive lesion of an increasing clinical importance. Individual risk assessment is essential for an optimal treatment. Our objective was to identify clinical and molecular characteristics of a subgroup of DCIS with an unfavorable prognosis. Methods: In a population study, we analyzed women with DCIS diagnosed within one mammography screening unit. In the experimental part of this work, we conducted a comparative analysis of five biological markers in normal tissue, DCIS and invasive breast cancer by means of gene expression analysis and analysis of loss of heterozygosity (LOH). Results: We demonstrated a high proportion of pure (no invasive component) DCIS (14.41%) of all breast lesions described as malignant. In our sample, we saw a homogeneous distribution of risk factors without noting a clear pattern identifying high-risk subtypes. We noted significant differences in clinical management of tumors with similar characteristics, which demonstrates the present state of limited use of clinical predictors. In the laboratory experiment, we showed differences in loss of heterozygosity (LOH) between DCIS and invasive breast cancer for BRCA1 (8.69% vs. 44.74%) and BRCA2 (9.52% vs. 45.0%). In contrast, we did not find any differences for p53 (31.82%...
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Molecular characteristics of ductal carcinoma in situ, and their clinical impact
Böhm, Jan ; Zikán, Michal (advisor) ; Dundr, Pavel (referee) ; Strnad, Pavel (referee)
Objectives: Ductal carcinoma in situ (DCIS) is a non-invasive lesion of an increasing clinical importance. Individual risk assessment is essential for an optimal treatment. Our objective was to identify clinical and molecular characteristics of a subgroup of DCIS with an unfavorable prognosis. Methods: In a population study, we analyzed women with DCIS diagnosed within one mammography screening unit. In the experimental part of this work, we conducted a comparative analysis of five biological markers in normal tissue, DCIS and invasive breast cancer by means of gene expression analysis and analysis of loss of heterozygosity (LOH). Results: We demonstrated a high proportion of pure (no invasive component) DCIS (14.41%) of all breast lesions described as malignant. In our sample, we saw a homogeneous distribution of risk factors without noting a clear pattern identifying high-risk subtypes. We noted significant differences in clinical management of tumors with similar characteristics, which demonstrates the present state of limited use of clinical predictors. In the laboratory experiment, we showed differences in loss of heterozygosity (LOH) between DCIS and invasive breast cancer for BRCA1 (8.69% vs. 44.74%) and BRCA2 (9.52% vs. 45.0%). In contrast, we did not find any differences for p53 (31.82%...
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Importance of HSD17B1 gene amplification in breast cancer
MAŠOVÁ, Michaela
Breast cancer is the most common female tumour disease. Although, the incidence is constantly growing, mortality of this disease is decreasing. However, there are still occurrences, where the conventional therapy failed. One of the important therapeutic attribute is hormone dependence of breast cancer and status of growth factor receptor HER2 (Her-2/neu, c-erbB-2). Treatment of the breast cancer with higher expression of estrogene or progesterone receptors (ER or PR) could be targeted-into blockade of these receptors or in the case of HER2 we could blockade it´s function with monoclonal antibody trastuzumab or lapatinib. Because of aggression of HER2 positive tumour cells, this subtype of breast cancer belonged to the group of patients with the worst prognosis. Thanks to targeted (biological) therapy belongs this patients into the group with the best treatable breast cancer today. However, in some of the hormone-dependent breast cancer cases the treatment fails. One of the reasons could be the product of HSD17B1 gene that is involved in metabolism of these hormones. Moreover, this gene is localized on chromosome 17 (like HER2 gen) and therefore it´s aberration could be suspected. Because the FISH probe for HSD17B1 gene is not commercially available, we prepared it by using transgenic E. coli bacterial clones. The specifity was checked on chromosomal spreads. In this presented thesis, we investigated 50 patient´s breast cancer samples by using fluorescent in situ hybridization to determine the status of HSD17B1 gene. Amplification of the gene could be important in the treatment of breast cancer and in resistance to antihormonal therapy. Next, we tried to check, if the status of HSD17B1 gene could be dependent on status of HER2 gene or if it correlates for example with patient´s age at time of diagnosis etc. Although, the statistical important correlations were not found, it seems, that HSD17B1 gene is lightly increased in some cases. In the next phase the study will be extended of another patient samples and the clinical dates and analysis in relation to HSD17B1 will be done. This is a pilot project. The main goal was to prepare HSD17B1 gene probe intended for commercialization and check the probe on the set of patients with breast cancer.
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