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

Departments of Neurosurgery [S.L., D. A. B.], Pathology [D. T.], and Human Genetics [A. W., T. J. M. H.], Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands

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 satellitosis. The tumors were examined for loss of heterozygosity with markers from chromosomes 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.

¹ Supported in part by Dutch Praeventiefonds Grant 28-1839.

² To whom requests for reprints should be addressed.

Received 6/21/91. Accepted 1/ 8/92.

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