Fibroblast growth factor receptor 3 gene (FGFR3) mutations in high-grade muscle-invasive urothelial bladder cancer in a Brazilian population: evaluation and prevalence

Abstract

Objective: To understand the feasibility of FGFR3 tests in the Brazilian public health context, and to sample the mutational burden of this receptor in high-grade muscle invasive bladder cancer. Methods: A total of 31 patients with high-grade muscle-invasive bladder cancer were included in the present study. Either transurethral resection of bladder tumor or radical cystectomy specimens were analyzed. Formalin-fixed paraffin-embedded tissue blocks were sectioned, hematoxylin and eosin stained, and histologic sections were reviewed. Total RNA was extracted using the RNeasy DSP formalin-fixed paraffin-embedded kit. Qualitative results were displayed in Rotor-Gene AssayManager software. Results: Six patients were excluded. From the samples analyzed, four (16.7%) were considered inadequate and could not have their RNA extracted. Two patients presented FGFR3 mutations, accounting for 9.5% of material available for adequate analysis. The two mutations detected included a Y373C mutation in a male patient and a S249C mutation in a female patient. Conclusion: FGFR3 mutations could be analyzed in 84% of our cohort and occurred in 9.5% of patients with high-grade muscle invasive bladder cancer in this Brazilian population. FGFR3 gene mutations are targets for therapeutic drugs in muscle-invasive bladder cancer. For this reason, know the frequency of these mutations can have a significant impact on public health policies and costs provisioning.

FGFR families: biological functions and therapeutic interventions in tumors

“…249,250 Bladder cancer is the most frequently occurring tumor with FGFR3 mutations, with an incidence of 9−11%. [251][252][253] In bladder cancer, activation of the SRC pathway by FGFR3 leads to resistance of tumor cells to FGFR inhibitors, such as infigratinib or erdafitinib. 254 FGFR3 upregulates ETS translocation variant 5 (ETV5) via the MAPK/ERK pathway, leading to elevated transcriptional coactivator with PDZ-binding motif (TAZ), a cotranscriptional regulator of the Hippo signaling pathway involved in cell contact inhibition, which promotes the proliferation of bladder cancer cells.…”

“…Bladder cancer is the most frequently occurring tumor with FGFR3 mutations, with an incidence of 9−11% 251–253 . In bladder cancer, activation of the SRC pathway by FGFR3 leads to resistance of tumor cells to FGFR inhibitors, such as infigratinib or erdafitinib 254 .…”

The CABEM Initiative: Saving Patients With Muscle-invasive Bladder Cancer

“…The higher survival rate has also resulted in nurses having more experience in caring for patients with ostomies and oncologists developing greater expertise in treating MIBC, including NAC, adjuvant, and palliative care. We could also improve the recruitment of our research unit [6,7], and we are nowadays the top recruiter center of some of the international trials on bladder cancer in Brazil.…”