Open AccessFibroblast 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
Author(s) -
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
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01334.x
Subject(s) - bladder cancer , urine , fibroblast growth factor receptor 3 , medicine , urine cytology , tumor marker , pathology , mutation , cancer research , cancer , urology , biology , receptor , fibroblast growth factor , gene , biochemistry
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)