Microglia in Gemistocytic Astrocytomas

• Main Authors: F Geranmayeh, BW Scheithauer, MB Graeber
• Format: Article
• Language: English
• Published: Tehran University of Medical Sciences 2005-10-01
• Series: Iranian Journal of Public Health
• Subjects: Microglia; Gemistocytic astrocytomas
• Online Access: http://journals.tums.ac.ir/PdfMed.aspx?pdf_med=/upload_files/pdf/2467.pdf&manuscript_id=2467

Background: Gemistocytic astrocytomas behave more aggressively than other diffusely growing astrocytic tumours. They are characterised by a high mutation rate of the p53 gene and cytological as well as immunological abnormalities including frequent perivascular mononuclear infiltrates. Microglia are resident brain macrophage precursor cells that form a network of immune competent cells within the normal central nervous system. They are of increasing interest in the context of glioma growth. Material and Methods: We selected 23 tumour samples from among 201 samples obtained from patients with gemistocytic astrocytomas operated on at the Mayo Clinic between 1985 and 1998. These tumours have been previously analysed for p53 mutations, p53 protein and proliferative activity (Neurosurgery 48:187-194, 2001). Immunolabelling for three established microglial markers, CR3/43, Ki-M1P and iba1 was carried out on adjacent tissue sections. In addition radioactive in-situ hybridization was carried out. Results: A high number of microglial cells were detected in gemistocytic astrocytomas. More microglia were present when the fraction of gemistocytes was high (correlation coefficient= 0.740, P< .0000542). Varying numbers of gemistocytic tumour cells expressed MHC class II molecules. Importantly, the more class II immunoreactive gemistocytes were present, the fewer class II positive microglial cells could be detected (correlation coefficient= -0.623, P<0.00148). Conclusions: Our findings support the view that gemistocytic astrocytomas contain unusually high numbers of microglial cells. The finding of aberrant MHC class II expression by gemistocytic tumour cells correlating with a loss of immune competent, MHC class II expressing microglia sheds new light on the immunology of these tumours. We suggest that the findings reported here may be related to the especially poor prognosis of gemistocytic astrocytomas. It is well known that the proliferative potential of neoplastic gemistocytes is very low and it has remained an intriguing question as to why these tumours are so “successful” biologically. The fact that aberrant expression of MHC class II molecules by non-professional antigen presenters may induce T cell anergy could provide one explanation.