Molecular Characterization of Areas with Low Grade Tumor or Satellitosis in Human Malignant Astrocytomas1

Malignant astrocytomas often display histopathological heterogeneity. In the present study, we have molecularly characterized different areas within 4 such tumors to determine whether the tissue heterogeneity can be explained by differences in DNA constitution. Two tumors contained low grade areas, and the other 2 had areas with satellites». The tumors were examined for loss of heterozygosity with markers from chromo somes 9p, 10, and 17p and for amplification of the epidermal growth factor receptor gene. In each case, the high grade portion of the tumor displayed at least one of these structural alterations. However, identical alterations were found in the associated low grade or satellitosis areas of each tumor. Our data suggest that: (a) genetic alterations associated with tumor progression already occur in histopathologically low grade areas of high grade astrocytoma; (b) satellitosis associated with a high grade astrocytoma has to be considered as part of that tumor; and (c) tissue heterogeneity within a high grade astrocytoma is not a consequence of differences in DNA constitution at the loci that were examined. pathological grading and DNA constitution, we molecularly characterized 4 malignant astrocytomas of mixed composition. Two had distinct low grade portions of sufficient volume for DNA analysis. The other 2 contained extensive areas of reactive gliosis with satellitosis. Satellitosis is characterized by the typ ical grouping of neoplastic astrocytes around neurons when the tumor infiltrates the gray matter (17). The different samples of the tumors were analyzed for loss of chromosome 17p and for genetic alterations associated with tumor progression, i.e., loss of chromosomes 9p and 10 and EGFR gene amplification. Here we report that the molecular changes found in the high grade areas of the respective tumors were already present in their associated low grade or satellitosis areas. From this we conclude that histopathologically hetero geneous astrocytomas have the genetic features of their phenotypically most malignant area.