Glioblastoma multiforme in the microscope: Diagnostic features of importance for prognosis and treatment

Abstract: Glioblastoma multiforme (GBM) is the most malignant and also the most common form of brain tumour in humans. The overall aim of this thesis was to investigate morphological and diagnostics features in human GBM that may be of importance for prognosis and treatment. Immunohistochemically stained tissue sections have been microscopically analysed regarding immuno-reactive cells, cell proliferation, telomerase activity and presence of coxsackie adenovirus receptor (CAR). While telomerase activity reflects inherent life prolongation, CAR act as adhesion molecules on target cells in adenoviral based gene therapy. We found that cytotoxic T-lymfocytes (CTL) occurred spontaneously in GBM but also that a transient increase was detected after immunotherapy. Macrophage positive cells were in general plentiful. GBM as well as other grades of gliomas, expressed low levels of CAR while neuroblastomas and medulloblastomas exhibited a high CAR expression. However, various regions and cell types of the normal brain also expressed CAR. Proliferation activity (Ki-67) showed a significant correlation to longer survival if index was below 10 %, while telomerase activity (hTERT) showed no relation to length of survival. Different methods of assessment of Ki-67 are of relevance for histopathological diagnostics. This project indicates that morphological features of importance for prognosis and treatment can be identified by the use of established and simple, reliable methods, routinely applied in clinical pathological diagnostics.