Major Histocompatibility Class-I (MHC-I) downregulation in glioblastoma is a poor prognostic factor but not a predictive indicator for treatment failure

Nadeem S Butt; Maher Kurdi; Motaz M Fadul; Sahar Hakamy; Bassam M J Addas; Eyad Faizo; Shadi Alkhayyat; Ahmed K Bamaga; Taghreed Alsinani; Yousef Katib; Fahad Okal; Yazid Maghrabi; Abdulrahman J Sabbagh; Rana Moshref; Sultan Albalawi; Alaa Alkhotani; Fawaz Mohammed; Nasser Mulla; Saleh Baeesa

doi:10.1016/j.prp.2023.154816

Major Histocompatibility Class-I (MHC-I) downregulation in glioblastoma is a poor prognostic factor but not a predictive indicator for treatment failure

Pathol Res Pract. 2023 Oct:250:154816. doi: 10.1016/j.prp.2023.154816. Epub 2023 Sep 9.

Authors

Nadeem S Butt¹, Maher Kurdi², Motaz M Fadul¹, Sahar Hakamy³, Bassam M J Addas⁴, Eyad Faizo⁵, Shadi Alkhayyat⁶, Ahmed K Bamaga⁷, Taghreed Alsinani⁸, Yousef Katib⁹, Fahad Okal¹⁰, Yazid Maghrabi¹¹, Abdulrahman J Sabbagh⁴, Rana Moshref¹¹, Sultan Albalawi¹², Alaa Alkhotani¹³, Fawaz Mohammed¹, Nasser Mulla¹⁴, Saleh Baeesa¹¹

Affiliations

¹ Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia.
² Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia. Electronic address: [email protected].
³ Neuromuscular Unit, King Fahad Medical Research Center, Jeddah, Saudi Arabia.
⁴ Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Department of Surgery, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia.
⁶ Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University and Hospital, Jeddah, Saudi Arabia.
⁷ Department of Paediatric, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
⁸ Department of Neurosurgery, King Fahad General Hospital, Jeddah, Saudi Arabia.
⁹ Department of Radiology, Faculty of Medicine, Taibah University, Madinah, Saudi Arabia.
¹⁰ Section of Neurosurgery, Department of Surgery, King Abdulaziz Medical City, National Guard Hospital Affairs, Jeddah, Saudi Arabia.
¹¹ Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
¹² Department of Surgery, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
¹³ Department of Pathology, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
¹⁴ Department of Internal Medicine, Faculty of Medicine, Taibah University, Medina, Saudi Arabia.

PMID: 37725880
DOI: 10.1016/j.prp.2023.154816

Abstract

Background: MHC-I expression is a crucial factor in cancer immunity, and its regulations can impact tumor progression and recurrence. The mechanism through which glioblastoma use MHC-I to avoid immunosurveillance has been rarely investigated.

Methods: A retrospective cohort of 35 patients with IDH-mutant WHO-Grade 4 astrocytoma and IDH-wildtype glioblastoma were examined for MHC-I using protein and gene expression assays. The association between IDH mutation, TP53 mutation, and MHC-I expression with recurrence-free interval were investigated.

Results: The average patients' age was 49.6 year. IDH was wildtype in 13 tumors. MHC-I protein expression was absent in 30 tumors, faint in 4 tumors, and membrane bound dense expression in single tumor. MHC-I expression was upregulated in 10 tumors and 25 tumors showed MHC-I downregulation. P53 was positively expressed in 19 cases and lost in 13 cases. A significant statistical difference was observed in the RFI between tumors with distinct MHC-I expression and IDH-mutation [p-value = 0.008]. IDH-wildtype tumors with upregulated MHC-I expression showed late tumor recurrence compared to IDH-wildtype tumors with downregulated MHC-I expression. There was insignificant statistical difference in RFI among patients with varying degree of MHC-I expression, who received TMZ or TMZ and other chemotherapies [P-value = 0.44] CONCLUSIONS: Glioblastoma with upregulated MHC-I showed a delayed tumor recurrence in comparison to those with downregulated MHC-I expression. However, downregulated MHC-I may not necessarily be an indicator of poor problems.

Keywords: Glioblastoma; MHC-I; Recurrence; TP53; WHO Grade 4 Astrocytoma.