Expression of tumoral GSK3-β, PD-L1, and CD8 cell density in urothelial carcinomas, association with tumor grade and overall survival

Bladder cancer is the most common malignancy in the urinary tract, and is biologically and clinically quite heterogeneous. Around 90% of diagnoses are made in the 6th decade, being more prevalent in males. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) axis play a putative role in immune checkpoint and as a means through which cancer evades the immune system. Inhibition of the glicogênio synthase kinase (GSK) 3 leads to the downregulation of PD-1 via upregulation of the transcription factor Tbet. The use of biomarkers PD-L1 and GSK-3β and evaluation of the immune infiltrate have very promising correlations with urothelial carcinoma prognosis and treatment prediction.OBJECTIVETo investigate the protein expression of PD-L1 and GSK-3β and the CD8-positive immune infiltrates in bladder carcinomas.MATERIALS AND METHODSThis was a cross-sectional study of 140 samples of urothelial carcinomas from 2015 to 2018. Automated digitally assisted scoring and conventional analyses of the markers of GSK-3β (27C10), CD8 (7103β) and PDL-1 (22c3), were reviewed by two pathologists independently and a histologic score was calculated. The density of CD8 was also measured.RESULTSThe immunoexpression of GSK-3β (91%) was presented in most samples, PD-L1 in 62.9% and CD8 cells present in 46.3% of cases. When analyzed in conjunction, the levels of GSK-3β and PD-L1 (P = 0.033), and CD8 and PD-L1 (P