Programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) expression in bladder cancer (BC): Differences in recurrent, progressive, and metastatic disease.

Abstract

e16001 Background: The significance of PD-L1/PD-1 expression in BC is still unclear. In the present study we evaluated the PD-L1/PD-1 expression in tumor tissue (TT) and immune cells (IC) in the primary BC tumor as well as in case of BC recurrence and/or metastasis to detect possible changes in PD-L1/PD-1 expression using immunohistochemstry. Methods: PD-L1/PD-1 expression was determined in histological specimens of 20 pat. with a recurrent non-muscle invasive BC (NMIBC – Cohort 1) as well as in 20 pat. with muscle-invasive BC (MIBC- Cohort 2) treated by radical cystectomy and appearance of metastases during follow up using commercial available assays (E1L3N, Cell Signaling/ Zytomed). Staining intensity was performed using the Cologne Score. PD-L1/PD-1 status was compared between primary tumor and metastatic/recurrent/progressive BC tissue and correlated with clinical data. Results: Cohort 1: In NMIBC (18m,2f) a recurrent tumor occurred after 25 mo (1-114). In the recurrent TT PD-L1 expression was higher compared to primary BC in 15%. In case of progression higher PD-L1 expression was detectable in 42.9%. IC showed higher PD-L1 expression in 50% of recurrent NMIBC and in 42% in case of progression. PD-1 expression on IC rose in 70% in recurrent and 71% in progressive NMIBC without correlation to time interval of appearance. Cohort 2: After curative cystectomy (17m,3f) metastases occurred after a median time of 20.5 mo (0-58). Comparing PD-L1 expression in cystectomy specimens and metastases we found differences in 52.9% (4x down/5x up). Expression of PD-L1 in primary BC tissue correlated significantly with the time to metastasis (p < 0.05). Conclusions: In case of metastasis after cystectomy as well as in recurrent/progressive NMIBC we found distinct variations in PD-L1/PD-1 expression in TT and IC. In MIBC primary PD-L1 status correlates with the time to metastasis. Whether PD-L1/PD-1 status can be helpful for clinical decisions (i.e. adjuvant therapy, instillation therapy) or as prognosticator have to be subject of further study.