PURPOSE: Fibroblast growth factor receptor 3 (FGFR3) mutations were
reported recently at a high frequency in low-grade urothelial cell
carcinoma (UCC). We investigated the feasibility of combining
microsatellite analysis (MA) and the FGFR3 status for the detection of UCC
in voided urine. EXPERIMENTAL DESIGN: In a prospective setting, 59 UCC
tissues and matched urine samples were obtained, and subjected to MA (23
markers) and FGFR3 mutation analysis (exons 7, 10, and 15). In each case,
a clinical record with tumor and urine features was provided. Fifteen
patients with a negative cystoscopy during follow-up served as controls.
RESULTS: A mutation in the FGFR3 gene was found in 26 (44%) UCCs of which
22 concerned solitary pTaG1/2 lesions. These mutations were absent in the
15 G3 tumors. For the 6 cases with leukocyturia, 46 microsatellite
alterations were found in the tumor. Only 1 of these was also detected in
the urine. This was 125 of 357 for the 53 cases without leukocyte
contamination. The sensitivity of MA on voided urine was lower for
FGFR3-positive UCC (15 of 21; 71%) as compared with FGFR3 wild-type UCC
(29 of 32; 91%). By including the FGFR3 mutation, the sensitivity of
molecular cytology increased to 89% and was superior to the sensitivity of
morphological cytology (25%) for every clinical subdivision. The
specificity was 14 of 15 (93%) for the two (molecular and morphological)
cytological approaches. CONCLUSIONS: Molecular urine cytology by MA and
FGFR3 mutation analysis enables a highly sensitive and specific detection
of UCC. The similarity of molecular profiles in tumor and urine
corroborate their clonal relation
