PD-L1 staining in patients’ samples may be prognostic of survival in glioblastoma
Date: 08 Sep 2017
Topic: Central nervous system malignancies / Pathology/Molecular biology
The intratumoural staining pattern of PD-L1 and the intensity of PD-1 staining in tumour infiltrating lymphocytes (TILs) emerged as potentially positive prognostic factors in patients with glioblastoma, according to findings from a retrospective analysis presented at ESMO 2017, the Annual Congress of the European Society for Medcial Oncology in Madrid, Spain.
Glioblastoma is the malignancy most commonly diagnosed within the brain and carries a poor prognosis.
Lead author Didem ?ener Dede, Associate Professor in the Department of Medical Oncology, Ankara Y?ld?r?m Beyaz?t Universtiy Faculty of Medicine in Ankara, Turkey and colleagues quantitated the degree of PD-L1 and PD-1 expression, as well as CD4-positive and CD8-positive TILs, and isocitrate dehydrogenase (IDH-1) mutation. In addition, they evaluated the value of expression levels as prognostic factors of response following surgery and chemoradiotherapy in patients with glioblastoma.
The retrospective study included 90 patients who were newly diagnosed with glioblastoma and underwent surgery between February 2006 to February 2017 at institutions throughout Ankara. PD-L1, PD-1 expression, CD4-positive and CD8-positive TILs, and IDH-1 mutation were assessed in the patients’ tumour specimens. IDH-1 mutation analysis was done by real time PCR, and PD-L1 and PD-1 levels were assessed by immunohistochemistry using the Ventana® antibody (clon-SP263, ROCHE).
For PD-1, PD-L1, CD4, CD8 TILs staining intensity was graded as low, moderate, dense and estimated in percents’ samples. The cut off value set ?5% staining as the threshold for PD-L1, PD-1 positivity.
The density of TILs in the intratumoral perivascular fields was positively associated with PD-L1 expression
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The study included 90 patients with glioblastoma having a mean (standard deviation) age of 57 (± 12.3) years and 63.3 % of the patients were male. Chemoradiotherapy plus chemotherapy with temozolamide following surgery had been admnistered to approximately half (53.3%) of patients.
Two different staining patterns of PD-L1 expression were described as diffuse fibrillary in 29 (32.2%) samples and membranous staining in 15 (16.7%) of samples. IDH-1 mutation was detected in 30 (33%) patients’ samples and dense PD-1 staining was seen. Intense staining of TILs in the perivascular field was observed, which, according to the authors, is rarely found in the intratumoral area.
By Kaplan Meier, Cox regression tests and SPSS 23, the density of TILs in the intratumoral/ perivascular fields positively associated with PD-L1 positivity (r=0.46; p< 0.0001). The intensity of TILs in perivascular areas was significantly lower in tumours that were negative for PD-L1 expression compared to PD-L1-positive tumours (p < 0.001).
No association was found between IDH-1, PD-L1, and TILs. No significant association was found between survival and sex (log rank p = 0.78), PD-L1 positivity (log rank p = 0.13), and IDH-1 mutation status (log rank p = 0.64).
The presence of dense perivascular PD-1-positive TILs was found to be a positive prognostic factor as was dense membranous PD-L1 staining, whereas advanced age emerged as a negative independent prognostic factor by multivariate analysis.
Conclusions
The authors concluded that the staining pattern of PD-L1 and the density of PD-1 expression in TILs may have prognostic importance in patients with newly diagnosed glioblastoma.
Disclosure
No external funding was reported.
Reference
326O – ?ener Dede D, et al. The association of programmed death-ligand 1 (PD-L1), programmed cell death (PD-1), tumor infiltrating lymphocytes (TILs) and isocitrate dehydrogenase (IDH-1) mutation in glioblastome multiforme
