Biologics: Targets & Therapy (Feb 2023)
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
Maher Kurdi,1,2 Nasser Mulla,3 Yousef Katib,4 Taghreed Alsinani,5 Sahar Hakamy,2 Bassam MJ Addas,6 Husam Malibary,7 Taher F Halawa,8 Marwa S Farhan,9 Eyad Faizo,10 Saleh Baeesa6 1Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia; 2Brain Tumour Unit, KFMRC, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Internal Medicine, Faculty of Medicine, Taibah University, Medina, Saudi Arabia; 4Department of Radiology, Faculty of Medicine, Taibah University, Madinah, Saudi Arabia; 5Department of Surgery, King Fahad General Hospital, Jeddah, Saudi Arabia; 6Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 7Department of Internal Medicine, Faculty of Medicine, King Abdul Aziz University, Jeddah, Saudi Arabia; 8Pediatric Hematology and Oncology Consultant, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia; 9Clinical Pathology Department, Cairo University, Cairo, Egypt; 10Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Tabuk University, Tabuk, Saudi ArabiaCorrespondence: Maher Kurdi, Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia, Tel +966 556655467, Email [email protected]: 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 IDH1R132 and IDH2R172 was examined using direct sequencing. The protein expression of CD204 on TAM was detected through immunohistochemistry.Results: IDH1R132 and IDH2R172 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: IDH1R132 or IDHR172 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.Keywords: WHO-grade 4 astrocytoma, IDH1/2 mutation, TAM, CD204, recurrence
