Background: The prediction of tumor malignancy is still one of the most demanding diagnostic tasks in urinary bladder cancer because of its clinicopathological heterogeneity. The aim of this study was to evaluate the expression of PD-L1 in tumor cells (TCs) and immune effector cells (IECs) as well as the pattern of distribution of PD-L1+ IECs within the tumor (dispersed or aggregated) and their association with survival of patients with pT1-pT4 urinary bladder cancer. Materials and methods: 110 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent radical cystectomy/cystoprostatectomy between 2011 and 2014 were included in the study. Paraffin blocks most representative of the tumor were selected for H&E staining as well as immunostaining with the use of rabbit anti-PD-L1 (Ventana clone SP142, Roche). In each sample, the area of the tumor containing PD-L1+ IECs, as well as, the pattern of distribution (dispersed or aggregated) of PD-L1+ immune effector cells within the tumor were analyzed. In addition, the expression of PD-L1 in TCs was also assessed. Results: Patients had a shorter survival time in pT2-pT4 cases without TCs expressing PD-L1 (p = 0.007) and/or when PD-L1+ IECs displayed a predominantly dispersed pattern of distribution (p = 0.013). Conclusions: The expression of PD-L1 on TCs and IECs is a prognostic factor which allows for stratification of patient survival in UBC. The predominance of dispersed or aggregated pattern of distribution of PD-L1+ IECs in the tumor may be considered as a new prognostic factor in pT1-T4 UBC and indicate the functional status of the immune system.

Background: Morbidity and mortality relating to urinary bladder cancer have remained largely unchanged for many years. Similarly, the five-year survival rate in this disease has not improved considerably. New developments in individualized therapy necessitate the search for novel factors that could predict the development of malignancy in UBC. In this study, we provide the first evidence that the expression of ROR alpha transcription factor influences the development of malignancy in UBC. Materials and methods: 105 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent cystectomy were included in the study. 4 µm tissue samples were stained immunohistochemically with a polyclonal anti-RORa antibody. The expression of RORa by the tumor cells (TCs) was assessed by counting TCs with a cytoplasmic and/or nuclear staining for RORa per 1000 TCs. The association between the extent of RORa expression and non-classic differentiation, tumor advancement (pT), grade (G) and regional lymph node spread was analyzed. Results: The cytoplasmic expression of RORa was detected in near all analyzed tumor samples (104/105). The extent of RORa expression was significantly higher in tumors which were more malignant with more propensity for non-classic differentiation and lymph node metastasis. We noted a lower percentage of TCs expressing RORa in poorly differentiated tumors (G3), compared to tumors moderately and higher differentiated (G1/G2). Conclusions: Our results suggest that RORa may play a significant role in the progression of urinary bladder cancer. RORa has a broad spectrum of regulatory activity relating to cell and tissue differentiation the mechanism of which is not fully understood. This study represents another step in the process of understanding the mechanisms of RORa regulation and highlights its potential role as a therapeutic target in urothelial bladder cancer.

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Background: The basic diagnostic tool of urinary bladder cancer is the histopathological assessment. However, it is insufficient to accurately predict the progression of this disease. There is a need to look for new prognostic factors that will make the therapeutic process more effective. The aim of this study is to evaluate the effect of activation of a PD1-PD-L1 immune checkpoint in immune effector cells (IECs) and tumor cells, on the development of malignancy in the form of non-classic differentiation in urinary bladder cancer. Materials and methods: 110 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent radical cystectomy/cystoprostatectomy between 2011 and 2014 were included in the study. Tumor advancement (pT stage), grade (G), as well as, non-classic differentiation frequency and number were evaluated pathologically. In each case, the area of the tumor containing PD-L1+ IECs was analyzed. The distribution of PD-L1+ immune effector cells within the tumor was also assessed as dispersed or aggregated. Results: The frequency of non-classic differentiation was significantly lower in urothelial bladder cancer tumors with a dispersed pattern of distribution of PD-L1+ IECs. A correlation between the extent of PD-L1 expression in tumor cells and the non-classic differentiation number in UBC was identified. Conclusions: The distribution of cells expressing the immune checkpoint biomarker PD-L1 constitutes a new prognostic factor and may play a key role in the selection of individualized immunotherapy. In addition, the evaluation of non-classic differentiation in the tumor may complement the assessment of PD-L1 expression due to its capacity to characterize the current malignant potential of the tumor, whereas the assessment of extent and distribution of PD-L1+ in tumor-associated immune cells indicates the functional status of the immune system.