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.
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 >or=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.
Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, 4-9-13 Yonan, Utsunomiya, Japan.
Makito
M
Miyake
Kokichi
K
Sugano
Hitomi
H
Sugino
Kazuho
K
Imai
Eri
E
Matsumoto
Koshi
K
Maeda
Shinich
S
Fukuzono
Hiroki
H
Ichikawa
Kiyotaka
K
Kawashima
Kaoru
K
Hirabayashi
Tetsuro
T
Kodama
Hiroyuki
H
Fujimoto
Tadao
T
Kakizoe
Yae
Y
Kanai
Kiyohide
K
Fujimoto
Yoshihiko
Y
Hirao
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000652:urine
C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3