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

APMIS. 2022 Aug;130(8):498-506. doi: 10.1111/apm.13249. Epub 2022 Jun 15.

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.

Keywords: Descriptive study; FGFR aberrations; PD-L1 expression; urothelial carcinomas.

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Transitional Cell* / genetics
  • Carcinoma, Transitional Cell* / metabolism
  • Carcinoma, Transitional Cell* / pathology
  • Denmark
  • Humans
  • Mutation
  • Receptor, Fibroblast Growth Factor, Type 3* / genetics
  • Receptor, Fibroblast Growth Factor, Type 3* / metabolism
  • Retrospective Studies
  • Urinary Bladder Neoplasms* / pathology

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3