Holman, R. (Rian) (2012) Expression of Epac and β-catenin in neuroblastoma tissue. thesis, Medicine.
Full text available on request.Abstract
Neuroblastoma is the most diagnosed extracranial solid tumor in early childhood. The tumor develops from precursor cells of the neural crest called neuroblasts. Although intensified therapy has improved the disease outcome during the past decades, the prognosis of the high risk tumors is still poor. Better understanding of the mechanisms underlying high risk neuroblastoma cases is needed to improve therapy options. Different pathways that are involved in normal development of the sympathetic nervous system are thought to play a role in neuroblastoma development. β-catenin is known to have a proliferative and anti-differentiative function in developing tissues. Furthermore, the cAMP pathway has a wide spectrum of functions in cells, but is also indicated to promote β-catenin signaling. In this study we aimed to elucidate the role of both β-catenin and the cAMP signaling pathway by its effector epac1 in the clinical behavior of neuroblastoma. A database containing 81 neuroblastoma patients who were diagnosed during the past three decades was developed. The expression of β-catenin and epac1 was investigated by applying immunohistochemistry to tumor sections of 39 of these neuroblastoma patients. After staining the tumors, a visual analog scale was developed to classify tumors according to the expression of epac1 and β-catenin. In contrast to what we expected, we were unable to detect β-catenin in neuroblastoma cell nuclei. The neuropil, however, showed various degrees of β-catenin expression. No significant relation was found between expression of β-catenin and risk group membership. Moreover, no significant differences were found for survival rates between β-catenin expression groups, although a trend was seen in survival curves indicating that high β-catenin expression was related to a higher mortality rate. Epac1 was diffusely expressed in the tissues and cell compartments. Different intensities of expression were seen in neuropil, cytoplasm and nuclei. High expression of epac1 in neuropil seemed to be protective for disease outcome. However, no significant relations were found between expression in neuropil, cytoplasm or nuclei and risk groups or survival. This study could implicate that upregulated β-catenin expression in neuroblastoma might have a negative effect on survival. Additional research with a higher power and a more representative tumor selection is required to validate our findings. Further research is needed as well to confirm a protective role of epac1 in neuropil, that we propose based on interpretation of our results
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Faculty Supervisor and Bont, Eveline de MD PhD Professor and Head division of pediatric oncology/hematology and Beatrix children hospital and University Medical Center Groningen and Jansen, Sepp PhD and Department of pediatric oncology and Department of molecular pharmacology and University Medical Center Groningen |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:49 |
| Last Modified: | 25 Jun 2020 10:49 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1067 |
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