Turkish Neurosurgery
Clinicopathological and prognostic significance of Tim-3 and Rel-B expression in grade 4 diffuse gliomas
Fatih Yilmaz1, Evrim Yilmaz1, Deniz Arik1, Funda Canaz1, Bulent Yildiz2, Melek Akcay3, Emre Ozkara4, Cengiz Bal5
1Eskisehir Osmangazi University Medical Faculty, Pathology, Eskişehir,
2Eskisehir Osmangazi University Medical Faculty, Medical Oncology, Eskişehir,
3Eskisehir Osmangazi University Medical Faculty, Radiation Oncology, Eskişehir,
4Eskisehir Osmangazi University Medical Faculty, Neurosurgery, Eskişehir,
5Eskisehir Osmangazi University Medical Faculty, Biostatistics, Eskişehir,
DOI: 10.5137/1019-5149.JTN.43568-23.2

Aim:This study aims to assess the clinicopathological and prognostic significance of Tim-3, an immune checkpoint molecule, and Rel-B, an NF-κB subunit, in grade 4 diffuse glioma samples and their relationship with each other. Material and Methods:The demographic, radiologic, prognostic, and treatment data of patients diagnosed with grade 4 diffuse glioma between 2016 and 2019 were reviewed and recorded. Tim-3 and Rel-B were applied to the paraffin-embedded tissues by immunohistochemistry method. Tim-3 expression was grouped as immunoreactivity density score (IDS) (Low, High) and expression percentage (<12%, >12%), while Rel-B expression was divided into positive and negative groups. Results:99 grade 4 diffuse glioma samples were detected, 8 of which were IDH-1 positive. Tim-3 was expressed only in immune cells around and inside the tumoral tissue, and expression was detected only in tumoral cells with Rel-B. Tim-3 IDS was found at lower levels (median 31.8) in IDH-1 positive cases and higher (median 158) in IDH-1 negative ones (p=0.020). A significant correlation was found between the Tim-3 IDS high group and Rel-B positivity (p=0.007). In the IDH-1 negative cohort, the univariate analysis revealed higher Tim-3 expression percentage and higher IDS were associated with better overall survival (OS) (p=0.041 and p=0.042 respectively) and progression-free survival (PFS) (p=0.023 and p=0.029 respectively), while in the multivariate analysis higher Tim-3 expression percentage was found to be an independent predictor for better OS (p=0.008) and PFS (p=0.022). Rel-B positive cases exhibited longer OS and PFS but the result was not statistically significant (p>0.05). Conclusion:Tim-3 can be a good prognostic predictor and treatment candidate, especially in patients with IDH-1 negative grade 4 diffuse gliomas however, further studies with more cases are needed for Rel-B. The significant relationship between Tim-3 and Rel-B expressions supported the interaction between NF-κB and immune checkpoint pathways.

Corresponding author : Fatih Yilmaz