MOLECULAR NEUROPATHOLOGY OF ASTROCYTIC BRAIN-TUMORS

Both surgical and molecular neuropathologists have recently achieved r emarkable progress in the histogenetic classification and molecular ch aracterization of human gliomas. Major histopathological achievements in the revised WHO classification include the introduction of immunohi stochemical reagents for glial fibrillary acidic protein and for the p roliferation-associated antigens, the definition of glioblastoma multi forme as an astrocytic neoplasm and the recognition of the pleomorphic xantho-astrocytomas as a novel clinico-pathological entity. In molecu lar neuropathology, alterations of oncogenes and tumor suppressor gene s and their potential functions have been identified, microsatellite a nalyses have revealed novel loci for putative tumor suppressor genes a nd distinct molecular pathways for different tumor entities are beginn ing to emerge. Mutations in cell cycle regulatory genes are present in most glioblastomas and may account for their striking growth potentia l. Autocrine and paracrine growth factors and their respective protein tyrosine kinase receptors appear to contribute both to glial and endo thelial cell proliferation. In our contribution, we would like to focu s on astrocytic gliomas. Findings with potential diagnostic relevance include changes associated with malignant progression of low grade ast rocytomas, patterns of genetic alterations which allow to further diff erentiate histopathological entities such as the glioblastoma multifor me into genetically distinct subsets and mechanisms of tumor angiogene sis in malignant gliomas. One of the major tasks ahead is to establish correlations and relationships between histopathological, molecular a nd clinical data. This will require a long-term collaboration between molecular neuropathologists, neurosurgeons and clinical neuro-oncologi sts.