FGFR3 gene alteration and protein expression in upper urinary tract carcinoma: unsuitability of ureteroscopic biopsy specimens for FGFR3 RNA testing

Abstract

We aimed to evaluate the suitability of archival ureteroscopic (URS) biopsy specimens for fibroblast growth factor receptor 3 FGFR3) biomarker analysis in upper urinary tract urothelial carcinoma. Thirty-six patients with upper urinary tract urothelial carcinoma who underwent diagnostic URS and radical nephroureterectomy (RNU) were included. Among the 36 RNU-derived tissue specimens, 33 (92%) yielded valid FGFR3 RNA test results; the remaining three (8.3%) showed test failure because of undetectable amplification by reverse transcriptase-polymerase chain reaction. Of the 33 RNU specimens with valid amplification, eight (24%) had FGFR3 alterations. Of these eight specimens, two (25%) were valid for FGFR3 RNA testing; one showed positive concordance with the paired RNU specimen, whereas the other did not. The remaining six specimens (75%) showed test failure. Correlation analysis of FGFR3 immunohistochemical staining scores demonstrated a moderate positive correlation between RNU and paired URS specimens (Spearman’s ρ = 0.47, P = 0.004). Our findings indicate that URS biopsy specimens are unsuitable for FGFR3 RNA testing but may be useful for protein-based biomarker analysis when RNU specimens are unavailable.

Keywords

urothelial carcinoma / gene alteration / FGFR3 / RNA / upper urinary tract carcinoma / immunohistochemical staining / biomarker

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