Abstract 712P
Background
Bladder cancer is posing major clinical challenge one of the most common cancers. It is estimated that every year almost 550 thousand new cases is diagnosed worldwide. Fibroblast Growth Factor Receptor 3 (FGFR3) is considered as one of the most promising targets because of its essential role in the cancer cell proliferation, progression and angiogenesis. The study aimed was to analyze the frequency of the FGFR3 mutations in non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) and the comparison of various diagnostic methods enabling the precise selection of patients for targeted therapies.
Methods
The cohort of 190 patients with bladder cancer (74MIBC and 116NMIBC) diagnosed at Memorial Cancer Center was enrolled in the study. The cohort NMIBC was analyzed in 2 subgroups: low grade (64) and high grade (52). Test material was derived from formalin-fixed, paraffin-embedded (FFPE) tumors. Genetic changes were analyzed by the Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI TOF MS), Next Generation Sequencing (NGS), digital droplet PCR (ddPCR) and additionally by protein expression level using immunohistochemistry (IHC) for MIBC group.
Results
In patients with MIBC mutations in FGFR3 were detected in 4.05% of samples analyzed by MALDI TOF and in additional 20.93% of cases increased protein level was detected. NGS analyzes allowed for the selection of another 28.37% of pathogenic mutations. In the group NIMBC FGFR3 mutations were detected in 24.14% of 116 tested samples. The frequency of the FGFR3 mutations was higher in the LG group compared to the HG NMIBCs (28.12 and 19.23%, respectively). DdPCR method allowed the detection of additional 4 samples with mutations present at very low frequencies. The number of detected aberrations depended on the type of the analyzed tumor and used diagnostic method. High sensitivity of ddPCR as the most sensitive enabled detection of even single tumor cells containing the examined changes.
Conclusions
Our data suggest that in the process of selection of the patients who will benefit the most from targeted therapies, it is particularly important to select the appropriate molecular diagnostic method.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Celon Pharma S.A.
Disclosure
All authors have declared no conflicts of interest.