Low Rate of IDH1 R132H Mutation in Adult Non-Supratentorial Low and Intermediate Grade Diffuse Gliomas
Benjamin Ellezam, Lindsey Heathcock, Gregory N Fuller, Janet M Bruner, Kenneth D Aldape. University of Texas MD Anderson Cancer Center, Houston, TX
Background: Diffuse gliomas (DG) are most frequent in supratentorial locations; however, they also rarely occur in the brainstem, cerebellum and spinal cord. Minute biopsies from these sites are often challenging to interpret and could benefit from diagnostic ancillary studies. Isocitrate dehydrogenase 1 (IDH1) mutation status has been shown to help distinguish adult low grade DG from reactive gliosis or from different CNS tumors with overlapping histologic features; however, published data on IDH1 mutation status in DG have focused on supratentorial tumors which may not share the same biology as their non-supratentorial counterparts. The cumulative reported rate of IDH1 R132H mutation in grade II or III DG is up to 75%.
Design: We searched our archives for cases of adult grade II or III DG involving brainstem, cerebellum or spinal cord. Cases with available archived tissue were processed for mutant IDH1 R132H immunohistochemistry.
Results: Thirty-three cases had tissue available, including 14 from brainstem (6 diffuse astrocytomas (DA) and 8 anaplastic astrocytomas (AA)), 10 from cerebellum (2 DA, 1 low grade glioma and 7 AA) and 9 from spinal cord (4 DA, 3 AA and 2 oligodendrogliomas). The median age at diagnosis was 47 years (range 17-78). Remarkably, only 3 (9%) of 33 tumors were positive for mutant IDH1 R132H immunohistochemistry, including 2 (20%) of 10 in the cerebellum (2 AA) and 1 (7%) of 14 in the brainstem (1 DA). None of 9 spinal cord tumors were positive for the mutant protein.
Conclusions: In contrast to the high reported rate of IDH1 R132H mutation in supratentorial grade II or III DG, the rate in non-supratentorial cases appears very low, suggesting location-specific biology in these tumors. Genome-wide studies and mutation profiling are warranted to further explore that possibility and to exclude other IDH1/2 mutations. The low prevalence of IDH1 R132H mutation in non-supratentorial DG may limit its use as a diagnostic tool in this setting.
Tuesday, March 20, 2012 1:45 PM
Platform Session: Section F, Tuesday Afternoon