Mutations of Fibroblast Growth Factor Receptor 3 Gene
(FGFR3) in Transitional Cell Carcinoma of Urinary
Bladder in Thai Patients [Revision-2a]†
Jariya Jantip MSc*,
Montira Tanthanuch MD**, Samornmas Kanngurn MD***, Watid Karnchanawanichkul MD**,
Choosak Pripatnanont MD**, Surasak Sangkhathat MD, PhD****, Paramee Thongsuksai MD*,***
Affiliation :
† A part of this work has been presented and published in the proceedings of the ASEAN+3 Graduate Research Congress 2012,
March, 2012, Chiang Mai, Thailand.
* Department of Biomedical Science, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
** Division of Urology, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
*** Anatomical Pathology Unit, Department of Pathology, Faculty of Medicine,
Prince of Songkla University, Songkhla, Thailand
**** Tumor Biology Research Unit, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
Objective : Determine the incidence of FGFR3 mutations in Thai patients with bladder transitional cell carcinoma (TCC),
and evaluate their correlation with pathological characteristics.
Material and Method: One hundred twenty two frozen tissue samples from TCC patients were analyzed for mutations in
exons 7, 10, and 15 of FGFR3 by polymerase chain reaction and direct DNA sequencing.
Results : FGFR3 mutations were detected in 22 of 122 cases (18%) studied, all of which were found within previously
identified hotspots, including S249C (13 cases; 59%) and R248C (4 cases; 18%) in exon 7, and Y375C (5 cases; 23%) in
exon 10, but no mutations in exon 15. Sixty-five patients (53%) were categorized as non-muscle-invasive TCC (pTa-pT1).
The incidence of mutations is significantly higher in non-muscle-invasive tumors (28%) compared to the muscle-invading
group (7%) (p<0.01). Patients with grade (G) 1 TCC have significantly higher mutation frequency (40%) compared to
other grades (4%) (p<0.01). When T stage and grade were considered together, mutations were most commonly found in
Ta-T1/G1 TCC (18/45 cases, 40%). Mean follow-up period was 45.1 months. Two-year and four-year overall survival (OS)
was 70% and 56% respectively. Three-year OS in non-muscle-invasive TCC (80%) is significantly higher than that of muscle
invading TCC (41%) (p<0.01). However, three-year OS in cases with an FGFR3 mutation (73%) is not significantly different
from cases without a mutation (61%). In 16 cases with an FGFR3 mutation and recurrent disease, no mutations were
detected in metachronous disease.
Conclusion : The overall incidence of FGFR3 mutations in Thai patients with TCC was lower than similar reports from
other ethnic groups. In the presented cases, although FGFR3 mutations were frequently detected in low-grade, non-muscle-
invasive TCC, identical mutation was not conserved in metachronous disease, thereby precluding the use of this marker in
detection of tumor recurrence.
Keywords : Urinary bladder cancer, FGFR3, Transitional cell carcinoma
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