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

PURPOSE: 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.