Immunhistologische Charakterisierung maligner Veränderungen beim Glioblastoma multiforme

Immunhistologische Charakterisierung maligner Veränderungen beim Glioblastoma multiforme

Immunhistochemical characterisation of malignant changes in glioblastoma multiforme

Lee, Susan Magdalene

Dissertation

Angenommen am: 2014-12-10

Erschienen: 2014-12-04

Betreuer: Schulz-Schaeffer, Walter PD Dr.

Gutachter: Stockhammer, Florian PD Dr

Gutachter: Kramm, Christof Prof. Dr.

Zum Verlinken/Zitieren: http://hdl.handle.net/11858/00-1735-0000-0023-9950-8

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Englisch

This study presents the results of paraffin sections from human brain tumors that have been coloured by means of immunohistological staining. Different kinds of glial tumors were investigated: Astrocyte WHO °II, astrocyte WHO °III, astrocyte WHO °IV – also called glioblastoma multiforme (GBM) – and oligodendroglioma WHO °II. Immunohistological markers used for this study were: vimentin, as a marker for undiffereniated cells; GFAP, as a marker for more differentiated cells; p53 as a major gene for tumor suppression; nestin as a marker for so-called progenitor cells; and finally p75, as a stem cell marker; Three questions were proposed: 1. How does the antigene expression of GBM cells differ from other tumor cells of glial genesis with minor malignancy? 2. Is there a change of antigene expression within GBM cells over time? 3. Is there a change of antigene expression of GBM cells depending on treatment strategies (in this case: tumor debulking and adjuvant radiochemotherapy (RCT) versus tumor debulking without radiochemotherapy)? A significant rise of vimentin-, nestin- and p75-expression could be shown for GBM cells opposed to other glial tumor cells. GFAP–expression only rose from astrocyte WHO °III compared to GBM cells. Cell staining for p53 was scattered in all types of tumors. Evaluation of GBM biopsies over time proved no significant changes. The same can be stated for the application of different treatment strategies. However, certain shifts could be observed. Patients that had received tumor debulking and radiochemotherapy showed a decrease in GFAP-, p53- and nestin-expression, but higher vimentin- and p75-expression. Whereas cells from patients treated only by surgical tumor debulking had a decline in vimentin- and p75-expression. In summary it can be stated that there is a proportional increase concerning tumor malignancy and the expression of vimentin, nestin and p75. Observing GBM biopsies over time, treatment with radiochemotherapy seemed to function as a kind of selection process and foster stem cells. The number of undifferentiated cells rose whereas the number of more differentiated cells decreased under this kind of therapy. The results are put into perspective mentioning and discussing latest research in this field of investigation like stem cell theories and possible GBM genesis.

Keywords: glioblastoma; tumor stem cells; immunhistochemical markers