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ORIGINAL ARTICLE
Year : 2018  |  Volume : 1  |  Issue : 6  |  Page : 196-200

Histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild-type and mutant World Health Organization Grade II and III gliomas


1 Department of Neurosurgery and Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
2 Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands

Correspondence Address:
Dr. Pierre Alain Robe
Department of Neurosurgery and Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, 100 Leuvenlaan-Huispost G03. 124, Utrecht 3584 CX
The Netherlands
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/glioma.glioma_42_18

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Aim: This study aims to describe the immune infiltrations in low-grade glioma (LGG) with respect to their histological classification, isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation status and survival. Materials and Methods: The IDH1/2 status (mutant or wild-type) of 66 World Health Organization Grade II and III gliomas were defined using next-generation sequencing or multiplex ligation-dependent probe amplification. The immune infiltrates of these tumors (46 mutant IDH, 20 wild-type IDH) were assessed immunohistochemically using a panel of antibodies (CD3, CD4, CD8, FOXP3, CD20, CD68, and CD163). Confirmatory analyses were performed on a cohort of lower grade gliomas from the Cancer Genome Atlas (TCGA). Statistical analyses were performed with Mann–Whitney U-tests and Kaplan–Meier survival estimates. Results: There was no relation between the amount of CD3+, CD4+, CD8+, or CD20+ lymphocyte infiltration and IDH mutation status in the tumors. FOXP3+ T regulatory cell infiltrates were rare, but more frequent in IDH1/2 wild-type tumors (P = 0.046). While the presence of these cells did not correlate with overall survival, FOXP3 messenger RNA expression was associated with survival in a distinct cohort of LGG from the TCGA (P < 0.05). CD4+ lymphocyte infiltrates, on the other hand, tended to prevail in astrocytic tumors as compared to oligodendrogliomas (P = 0.056). While CD68 (M1) microglial/monocytic cells were equally abundant in IDH mutant and wild-type tumors, the presence of round, activated M1 CD68+ microglia significantly associated with a mutant IDH status (P = 0.015). Conclusion: FOXP3+ expression and activated CD68+ M1 cells associated with IDH status in LGG, and might contribute to their differential evolution.


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