1. The association and prognostic significance of programmed death-ligand 1 (PD-L1) and isocitrate dehydrogenase (IDH-1) mutation in glioblastome multiforme(GBM) patients
- Author
-
Bulent Yalcin, Didem Sener Dede, Kamile Silay, Burak Bilgin, Fatma Betul Asan, Mehmet Ali Nahit Sendur, Hayriye Tatlı Doğan, Sule Ayik, Berrak Gumuskaya, Mutlu Hizal, Arife Ulas, and Bulent Akinci
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Mutation ,biology ,business.industry ,Newly diagnosed ,Ligand (biochemistry) ,medicine.disease_cause ,Isocitrate dehydrogenase ,Oncology ,PD-L1 ,biology.protein ,medicine ,Cancer research ,business ,Programmed death - Abstract
e13536 Background: We aimed to assessed thePD-L1, PD-1 expression, TILs and IDH-1 mutation associations and their prognostic importance in GBM. Methods: Newly diagnosed and all were operated GBM patients who folllowed between February 2006 to February 2017 were included retrospectively in the study. We assessed the PD-L1, PD-1 expression, CD4(+) ve CD8(+)TILs, IDH-1 mutation in initial tumor specimens. Immunohistochemistry was performed using Ventana® antibody (clon-SP263, ROCHE) for PD-L1 and PD-1, real time PCR used for IDH-1 mutation analysis. Intensity was graded as low, moderate, dense for PD-1, CD4, CD8 TILs. PD-L1 evaluated in percents. The cutoff value assumed as ≥5% for PD-L1 positivity. We used Kaplan Meier, Cox regression tests and SPSS 23. Results: Fourty eight patients included in the study. The mean age was 54± 14,4 and 34 (70%) patients were male. Thirty (70 %) patients were received chemoradiotherapy with temozolamide and 20 (41%) of them also received chemotherapy.We identified two different staining pattern of PD-L1 expression as diffuse fibrillary [13(27%)] and membranous staining [14(29%)]. IDH-1 mutation was found in 30 (62%) patients. We found that TILs were more intensely located in the perivascular area than intratumoral area and in that TILs, PD-1 intensity were dense. We also found a correlation between the percentages of PD-L1 positivity and the density of TILs in the intratumoral and perivascular areas (p < 0,002, r = 0,46). The intensity of both TILs in perivascular areas were significantly lower in PD-L1 (-) tumors than in PD-L1 (+) tumors (p < 0,001). We didn’t find any association between IDH-1 and PD-L1 or TILs. According to survival and multivariate analysis; age, sex, PD-L1 positivity and IDH-1 mutation status did not appear to have a significant effect on survival. (log rank 0,08; 0,30; 0,89; 0,14 respectively) The presence of dense intratumoral CD8(+) and PD-1 (+)TILs were found as positive; advanced age and membranous PD-L1 staining was found as negative independent prognostic factors. Conclusions: Different staining pattern of PD-L1 in tumor tissue and PD-1 positivity in TILs may be a prognostic importance in GBM
- Published
- 2017
- Full Text
- View/download PDF