Fibroblast growth factor receptor 3 mutation in voided urine is a useful diagnostic marker and significant indicator of tumor recurrence in non-muscle invasive bladder cancer

摘要

The fibroblast growth factor receptor (FGFR)-3 gene encodes a receptor tyrosine kinase that is frequently mutated in non-muscle invasive bladder cancer (NMIBC). A sensitive and quantitative assay using peptide nucleic acid-mediated real-time PCR was developed for detecting FGFR 3 mutations in the urine samples and evaluated as a molecular marker for detecting intravesical recurrence of NMIBC in patients undergoing transurethral resection of bladder tumor. FGFR 3 mutation was examined in tumor tissues and serially taken pre- and postoperative urine sediments in 45 NMIBC patients with a median follow up of 32 months. FGFR 3 mutations were detected in 53.3% (24/45) of primary tumor tissues, among which intravesical recurrence developed in 37.5% (9/24) of cases. FGFR 3 mutation in the primary tumor was not a significant prognostic indicator for recurrence, while the proportion of FGFR 3 mutation (i.e. tumor cellularity was ≥11%) in the preoperative urine sediments was a significant indicator for recurrence in patients with FGFR 3 mutations in the primary tumors. FGFR 3 mutations were detected in 78% (7/9) of postoperative urine samples from recurrent cases with FGFR 3 mutations in the tumor, while no mutations were detected in the urine of 15 non-recurrent cases. Urine cytology was negative in all cases with FGFR 3 mutations in the primary tumors, while the sensitivity of cytological examination was as high as 56% (5/9) in cases showing wild-type FGFR 3 in the primary tumors. Urine FGFR 3 mutation assay and cytological examination may be available in the future as complementary diagnostic modalities in postoperative management of NMIBC. ( Cancer Sci 2009)