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.

*DNA Mutational Analysis, *Microsatellite Repeats, *Protein-Tyrosine Kinase, Adult, Aged, Aged, 80 and over, Carcinoma/diagnosis/*genetics/urine, Female, Humans, Loss of Heterozygosity, Male, Middle aged, Mutation, Receptor, Fibroblast Growth Factor, Type 3, Receptors, Fibroblast Growth Factor/*genetics/metabolism, Research Support, Non-U.S. Gov't, Urologic Neoplasms/diagnosis/*genetics/urine, Urothelium/pathology
hdl.handle.net/1765/10063
Clinical Cancer Research
Erasmus MC: University Medical Center Rotterdam

van Rhijn, B.W.G, Lurkin, I, Chopin, D.K, Kirkels, W.J, Thiery, J.P, van der Kwast, Th.H, … Zwarthoff, E.C. (2003). Combined microsatellite and FGFR3 mutation analysis enables a highly sensitive detection of urothelial cell carcinoma in voided urine. Clinical Cancer Research. Retrieved from http://hdl.handle.net/1765/10063