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

• Published in: Cancer science 2010-01, Vol.101 (1), p.250-258
• Main Authors: Miyake, Makito, Sugano, Kokichi, Sugino, Hitomi, Imai, Kazuho, Matsumoto, Eri, Maeda, Koshi, Fukuzono, Shinich, Ichikawa, Hiroki, Kawashima, Kiyotaka, Hirabayashi, Kaoru, Kodama, Tetsuro, Fujimoto, Hiroyuki, Kakizoe, Tadao, Kanai, Yae, Fujimoto, Kiyohide, Hirao, Yoshihiko
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Female; Humans; Male; Medical sciences; Middle Aged; Mutation; Neoplasm Recurrence, Local - diagnosis; Nephrology. Urinary tract diseases; Original; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Tumors; Tumors of the urinary system; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - urine; Urinary tract. Prostate gland
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2009.01334.x

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 FGFR3 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. FGFR3 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. FGFR3 mutations were detected in 53.3% (24/45) of primary tumor tissues, among which intravesical recurrence developed in 37.5% (9/24) of cases. FGFR3 mutation in the primary tumor was not a significant prognostic indicator for recurrence, while the proportion of FGFR3 mutation (i.e. tumor cellularity was ≥11%) in the preoperative urine sediments was a significant indicator for recurrence in patients with FGFR3 mutations in the primary tumors. FGFR3 mutations were detected in 78% (7/9) of postoperative urine samples from recurrent cases with FGFR3 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 FGFR3 mutations in the primary tumors, while the sensitivity of cytological examination was as high as 56% (5/9) in cases showing wild‐type FGFR3 in the primary tumors. Urine FGFR3 mutation assay and cytological examination may be available in the future as complementary diagnostic modalities in postoperative management of NMIBC. (Cancer Sci 2009)