Objective: Although gemistocytic astrocytomas are graded as World Health Organization II astrocytomas, they behave more aggressively than other astrocytomas. Their proliferative potential is low, and it remains an intriguing question why these tumors are so biologically "successful." They show a high mutation rate of the P53 gene, cytological abnormalities, and frequent perivascular mononuclear infiltrates. Microglial cells, a feature of this astrocytoma variant, are of increasing interest in the context of glioma growth.
Methods: We selected 23 tumor biopsies from 201 samples obtained from patients with gemistocytic astrocytomas operated at Mayo Clinic between 1985 and 1998. These tumors were formerly analyzed for P53 mutations, p53 protein, and proliferative activity (). Immunolabeling for three microglial markers, including CR3/43, Ki-M1P, and iba1, was performed on adjacent tissue sections. In addition, in situ hybridization for the alpha-chain of the major histocompatibility complex (MHC) Class II molecule recognized by the CR3/43 monoclonal antibody was performed.
Results: A high number of microglia was detected in gemistocytic astrocytomas. More microglia were present if the fraction of gemistocytic tumor cells was high (correlation coefficient = 0.699; P < 0.0002). Interestingly, a number of gemistocytes were immunoreactive for MHC Class II molecules, an observation confirmed by in situ hybridization. Importantly, the higher the number of Class II immunoreactive gemistocytes, the fewer Class II positive microglial cells could be detected (correlation coefficient = -0.5649; P < 0.005).
Conclusion: Our results support the view that gemistocytic astrocytomas contain unusually high numbers of microglial cells. We propose that the finding of aberrant MHC Class II expression by gemistocytic tumor cells correlates with a loss of immune-competent MHC Class II-expressing microglia. This may be related to the especially poor prognosis of gemistocytic astrocytomas for which induction of T cell anergy could provide one explanation.