Accumulation of genetic changes is associated with poor prognosis in grade II astrocytomas.

Unexpectedly aggressive clinical course of some grade II astrocytomas is a diagnostic dilemma for routine histopathology. Because increasing tumor malignancy is a consequence of progressive accumulation of chromosomal alterations, we investigated whether aggressive behavior of grade II astrocytomas could be predicted by the number and type of gross chromosomal aberrations. We used comparative genomic hybridization to analyze 11 grade II astrocytomas with typical (good, n = 7) or poor (n = 4) prognosis. The results were also compared with a reference material of 13 grade III-IV astrocytomas and nine established cell lines. We found a median of two aberrations (range 0 to 4) in tumors with good prognosis and of 15.5 changes (range 8 to 28) in tumors with poor prognosis. Chromosomal gains were present in both groups, whereas chromosomal losses were frequent in tumors with poor prognosis (median 9.5, range 3 to 14) but rare in tumors with good prognosis (range 0 to 2). All chromosomal gains were also found in the high-grade astrocytoma group and the majority of them in cell lines. Chromosomal losses in grade II astrocytomas with poor prognosis were very similar to those in grade III-IV astrocytomas and cell lines. We conclude that an early accumulation of genetic changes in grade II astrocytomas is closely associated with poor patient prognosis, suggesting diagnostic use for comparative genomic hybridization in characterization of grade II astrocytomas.