Immunohistochemical Study of Bladder Cancer Molecular Subtypes and Their Association with PD-L1 Expression

• Published in: Cancers 2022-12, Vol.15 (1), p.188
• Main Authors: Goutas, Dimitrios, Palamaris, Kostas, Stofas, Anastasios, Politakis, Nektarios, Despotidi, Antonia, Giannopoulou, Ioanna, Goutas, Nikolaos, Vlachodimitropoulos, Dimitrios, Kavantzas, Nikolaos, Lazaris, Andreas C, Gakiopoulou, Hariklia
• Format: Article
• Language: English
• Subjects: Antibodies; Biomarkers; Bladder cancer; Cancer; Cancer therapies; Cloning; Cytokeratin; Diagnosis; DNA methylation; Drug delivery; Drug development; FDA approval; GATA-3 protein; Gene expression; Genetic aspects; Growth factors; Health aspects; Immune checkpoint; Immunohistochemistry; Immunosuppressive agents; Immunotherapy; Invasiveness; Ligands (Biochemistry); Medical prognosis; Metastasis; Mismatch repair; Mutation; Oncology, Experimental; PD-1 protein; PD-L1 protein; Phenotypes; Proteins; Tumors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15010188

The significant heterogeneity in clinical outcomes among patients with bladder cancer has highlighted the existence of different biological subtypes of muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Meanwhile, immune checkpoint proteins and their interference with tumor-related immune-evasive strategies has led to the development of several immunotherapeutic drugs targeting programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1). However, the lack of any known biomarker that could predict responses to immunotherapy has led to a more agnostic therapeutic approach. Here, we present a study conducted in 77 bladder cancer (BC) patients (n = 77), ranging from stages pTa to pT2. Tumor specimens were resected via transurethral resection of bladder tumor (TURBT) and consistuted of 24 low-grade (LG) and 53 high-grade (HG) tumors. Patients' tumors were then categorized into molecular subtypes, via immunohistochemistry (CK5/6 and GATA3). Furthermore, all tumor specimens were stained with anti-PD-L1 and demonstrated significant correlations with basal immunophenotype, stage pT2 and HG tumors. As such, we attempted to stratify patients into groups of likely-responders and likely-not-responders to immunotherapy with anti-PD-L1, based on their molecular phenotype. Finally, in acknowledging the fact that there is a universal lack of biomarkers associated with predicting BC response to immunotherapeutic drugs, we tested all tumors for deficiency of mismatch repair proteins (MMR).