Molecular neuropathology of astrocytic brain tumors

Both surgical and molecular neuropathologists have recently achieved remarkable progress in the histogenetic classification and molecular characterization of human gliomas. Major histopathological achievements in the revised WHO classification include the introduction of immunohistochemical reagents for glial fibrillary acidic protein and for the proliferation-associated antigens, the definition of glioblastoma multiforme as an astrocytic neoplasm and the recognition of the pleomorphic xantho--astrocytomas as a novel clinico-pathological entity. In molecular neuropathology, alterations of oncogenes and tumor suppressor genes and their potential functions have been identified, microsatellite analyses have revealed novel loci for putative tumor suppressor genes and distinct molecular pathways for different tumor entities are beginning to emerge. Mutations in cell cycle regulatory genes are present in most glioblastomas and may account for their striking growth potential. Autocrine and paracrine growth factors and their respective protein tyrosine kinase receptors appear to contribute both to glial and endothelial cell proliferation. In our contribution, we would like to focus on astrocytic gliomas. Findings with potential diagnostic relevance include changes associated with malignant progression of low grade astrocytomas, patterns of genetic alterations which allow to further differentiate histopathological entities such as the glioblastoma multiforme into genetically distinct subsets and mechanisms of tumor angiogenesis in malignant gliomas. One of the major tasks ahead is to establish correlations and relationships between histopathological, molecular and clinical data. This will require a long-term collaboration between molecular neuropathologists, neurosurgeons and clinical neuro-oncologists.