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

• Published in: Biologics Vol. 17; pp. 15 - 22
• Main Authors: Kurdi, Maher, Mulla, Nasser, Katib, Yousef, Alsinani, Taghreed, Hakamy, Sahar, Mj Addas, Bassam, Malibary, Husam, Halawa, Taher F, S Farhan, Marwa, Faizo, Eyad, Baeesa, Saleh
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2023; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Antibodies; Astrocytoma; Brain cancer; Cancer; cd204; Chemotherapy; Codon; Codons; DNA methylation; Genes; Genetic aspects; Gliomas; idh1/2 mutation; Immunohistochemistry; Macrophages; Medical research; Medicine, Experimental; Metabolism; Microenvironments; Mutation; Mutation hot spots; Original Research; Physiological aspects; recurrence; tam; Tumor microenvironment; Tumors; who-grade 4 astrocytoma; Saudi Arabia; United States > US; recurrence; TAM; IDH1/2 mutation; CD204; WHO-grade 4 astrocytoma
• ISSN: 1177-5475; 1177-5491; 1177-5491
• DOI: 10.2147/BTT.S394556

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.
The study included 20 samples of patients with WHO-grade 4 astrocytoma. The alteration hotspot in codon IDH1
and IDH2
was examined using direct sequencing. The protein expression of CD204 on TAM was detected through immunohistochemistry.
IDH1
and IDH2
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.
IDH1
or IDH
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.