E-ISSN: 1019-5157
ISSN: 2651-5024
Research
Prognostic Significance of Immune Checkpoint Molecules and Mismatch Repair Status in Meningiomas: A Clinicopathological Analysis of 200 Cases
Muserref Muge USTAOGLU✉ ,
Ismail SAYGIN ,
Emel CAKIR
Department of Pathology, Bayburt State Hospital, Bayburt, Turkey; Department of Pathology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey; Department of Pathology, Sancaktepe Martyr Prof. Dr. İlhan Varank Training and Research Hospital, İstanbul, Turkey
DOI: 10.5137/1019-5149.JTN.51847-26.2
Accepted: 18/09/2026
Article in Press
Corresponding Author:
Muserref Muge USTAOGLU (muge0392@hotmail.com)
Abstract
Aim
Meningiomas are among the most common primary tumors of the central nervous system, yet the clinicopathological and prognostic significance of immune checkpoint molecules in these tumors remains unclear. This study investigated the association of PD-1 and PD-L1 expression with clinicopathological features, overall survival, and mismatch repair (MMR) protein status.
Material and Methods
A retrospective analysis was conducted on a total of 200 meningioma cases, which included an equal number of WHO Grade 1 and Grade 2 tumors. Immunohistochemical staining was used to evaluate PD-1/PD-L1 and MMR protein expression, and their associations with histopathological parameters and overall survival were assessed.
Results
In 29% of cases, PD-L1 expression in tumor cells was detected. Although there was no significant clinical correlation between total PD-L1 expression and tumor grade, exclusive membranous PD-L1 staining was significantly associated with higher tumor grade (p = 0.002), brain invasion (p = 0.035), and spontaneous necrosis (p = 0.011). PD-1 positivity in tumor-infiltrating lymphocytes (TILs), observed in 12% of cases, was more prevalent in cases with brain invasion (p = 0.025). However, no definitive mismatch repair deficiency was identified, and MMR protein expression was preserved in 97% of cases. Kaplan-Meier analysis demonstrated that PD-L1 expression in TILs was associated with a shorter overall survival (HR: 2.456, 95% CI: 1.248-4.833, p = 0.009). This effect was attenuated after adjusting for age and WHO grade (HR: 1.805, 95% CI: 0.871-3.741, p = 0.112), with a borderline association in sensitivity analysis.
Conclusion
In meningiomas, membranous PD-L1 expression in tumor cells is associated with aggressive histopathological features. PD-L1 expression in TILs is linked to poorer survival in univariate analysis, although this association is attenuated following adjustment for age and WHO grade. These findings highlight the biological relevance of the tumor immune microenvironment but require validation in larger cohorts.
Meningiomas are among the most common primary tumors of the central nervous system, yet the clinicopathological and prognostic significance of immune checkpoint molecules in these tumors remains unclear. This study investigated the association of PD-1 and PD-L1 expression with clinicopathological features, overall survival, and mismatch repair (MMR) protein status.
Material and Methods
A retrospective analysis was conducted on a total of 200 meningioma cases, which included an equal number of WHO Grade 1 and Grade 2 tumors. Immunohistochemical staining was used to evaluate PD-1/PD-L1 and MMR protein expression, and their associations with histopathological parameters and overall survival were assessed.
Results
In 29% of cases, PD-L1 expression in tumor cells was detected. Although there was no significant clinical correlation between total PD-L1 expression and tumor grade, exclusive membranous PD-L1 staining was significantly associated with higher tumor grade (p = 0.002), brain invasion (p = 0.035), and spontaneous necrosis (p = 0.011). PD-1 positivity in tumor-infiltrating lymphocytes (TILs), observed in 12% of cases, was more prevalent in cases with brain invasion (p = 0.025). However, no definitive mismatch repair deficiency was identified, and MMR protein expression was preserved in 97% of cases. Kaplan-Meier analysis demonstrated that PD-L1 expression in TILs was associated with a shorter overall survival (HR: 2.456, 95% CI: 1.248-4.833, p = 0.009). This effect was attenuated after adjusting for age and WHO grade (HR: 1.805, 95% CI: 0.871-3.741, p = 0.112), with a borderline association in sensitivity analysis.
Conclusion
In meningiomas, membranous PD-L1 expression in tumor cells is associated with aggressive histopathological features. PD-L1 expression in TILs is linked to poorer survival in univariate analysis, although this association is attenuated following adjustment for age and WHO grade. These findings highlight the biological relevance of the tumor immune microenvironment but require validation in larger cohorts.
Keywords
Meningioma
immune checkpoint inhibitors
tumor microenvironment
prognosis
targeted therapy