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 chro mosomal alterations, we investigated whether aggressive behavior of gr ade 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 mate rial 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 goo d prognosis and of 15.5 changes (range 8 to 28) in tumors with poor pr ognosis. Chromosomal gains were present in both groups, whereas chromo somal 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 gr oup and the majority of them in cell lines. Chromosomal losses in grad e II astrocytomas with poor prognosis were very similar to those in gr ade III-IV astrocytomas and cell lines. We conclude that an early accu mulation of genetic changes in grade II astrocytomas is closely associ ated with poor patient prognosis, suggesting diagnostic use for compar ative genomic hybridization in characterization of grade n astrocytoma s.