PD‐L1 expression and FGFR‐mutations among Danish patients diagnosed with metastatic urothelial carcinoma: A retrospective and descriptive study

Abstract

Checkpoint inhibitors have changed the treatment landscape of advanced urothelial carcinoma (mUC), and recently, a fibroblast‐growth‐factor‐receptor (FGFR) inhibitor has been introduced. This study aimed at estimating programmed death‐ligand 1 (PD‐L1) expression in primary tumors (PTs) and the PD‐L1 expression concordance between PTs and paired metastases in 100 patients with UC managed in the real‐world setting. Further, the aim was to investigate FGFR1–3 aberrations and the correlation between FGFR1–3 aberrations and PD‐L1 expression. PD‐L1 immunohistochemistry was performed on 100 formalin‐fixed paraffin‐embedded archival primary UC samples and 55 matched metastases using the 22C3 PD‐L1 assay. PD‐L1 expression was determined by the combined positive score, considered positive at ≥10. Targeted next‐generation sequencing on the S5+/Prime System with the Oncomine Comprehensive Assay version 3 was used to detect FGFR1‐3 aberrations in PTs. We found that 29 of 100 PTs had positive PD‐L1 expression. The PD‐L1 concordance rate was 71%. FGFR1‐3 aberrations were observed in 18% of PTs, most frequently FGFR3 amplifications or mutations. We found no association between FGFR1‐3 aberrations and PT PD‐L1 expression (p = 0.379). Our data emphasize the need for further studies in predictive biomarkers.

PD-L1 expression in tumor and inflammatory cells is associated with favorable tumor features and favorable prognosis in muscle-invasive urothelial carcinoma of the bladder not treated by immune checkpoint inhibitors

“…For the PD-L1 assay used in this study, we had earlier demonstrated a similar staining behavior as for several established PD-L1 antibodies such as clones E1L3N, SP142, and SP263 [ 26 ]. It is of note that a high variability of PD-L1 data also exists in studies using the same antibodies [ 15 , 29 ]. The quantity of tissue analyzed per patient, section age and difficulties in the distinction of intraepithelial or peri-epithelial PD-L1 positive macrophages from true PD-L1 positive cancer cells might also contribute to the data diversity of PD-L1 IHC in the literature [ 26 , 35 , 36 ].…”