The Cancer Driver Genes IDH1 and IDH2 and CD204 in WHO-Grade 4 Astrocytoma: Crosstalk Between Cancer Metabolism and Tumour Associated Macrophage Recruitment in Tumour Microenvironment

Abstract

IDH1 and IDH2 are hotspot mutations commonly identified in WHO-grade 4 astrocytomas. Their association with TAMs has never been investigated. We aim to explore the crosstalk between the IDH1/2 mutation metabolic effect and TAMs in tumour microenvironment and how this relationship affects the tumour recurrence. Patients and Methods:The study included 20 samples of patients with WHO-grade 4 astrocytoma. The alteration hotspot in codon IDH1 R132 and IDH2 R172 was examined using direct sequencing. The protein expression of CD204 on TAM was detected through immunohistochemistry. Results: IDH1 R132 and IDH2 R172 were symmetrically identified as wildtype in 18/20 tumours (90%) and the remaining 2 tumours (10%) showed synonymous mutations on both codons. Tumours with IDH1/2-wildtype showed high expression of CD204 + TAMs in 10 cases and low expression in 8 cases. Typical expression was seen equally in IDH1/2 mutant tumours. There was no significant association between IDH1/2 and CD204 + TAM expression (p= 0.999). The association between the two groups was significantly observed among IDH-wildtype tumours (p=0.027). Highly expressed CD204 in IDH-wildtype tumours showed a median recurrence at 10 months compared to low CD204 expression, showed a median recurrence interval at 24 months. Conclusion: IDH1 R132 or IDH R172 has the same impact on the classification and prognosis of WHO-grade 4 astrocytoma. There was no crosstalk between IDH1/2 metabolic effect and CD204 + TAM. However, IDH-wildtype glioblastomas with dense CD204 + TAM are associated with early recurrence. Because the sample size is small, a larger study is recommended to determine the impact of IDH1/2 on TAMs.

Critical Response: “Does the Mutation of Cancer Driver Genes IDH1/2 and CD204 Influence Cancer Metabolism and Tumor Associated Macrophage Recruitment in Tumor Microenvironment” [Letter]

“…

We have reviewed and appreciated the work performed by Kurdi et al regarding the mutation in cancer driver genes IDH1/2 and CD204 and the correlation between mutations found in those genes and the alterations of tumor-associated macrophage recruitment in tumor microenvironment. 1 The IDH gene encodes a NADP(+)-dependent isocitrate dehydrogenase enzyme, which could be found in the cytoplasm and peroxisomes. Based on previous studies, IDH is an essential enzyme involved in major metabolic processes such as the TCA cycle, glutamine metabolism, adipogenesis, and redox regulation.

…”