A1 Refereed original research article in a scientific journal
Prognostic markers in invasive bladder cancer: FGFR3 mutation status versus P53 and KI-67 expression: a multi-center, multi-laboratory analysis in 1058 radical cystectomy patients
Authors: Mertens Laura S., Claps Francesco, Mayr Roman, Bostrom Peter J., Shariat Shahrok F., Zwarthoff Ellen C., Boormans Joost L., Abas Cheno, van Leenders Geert J.L.H., Götz Stefanie, Hippe Katrin, Bertz Simone, Neuzillet Yann, Sanders Joyce, Broeks Annegien, Peters Dennis, van der Heijden Michiel S., Jewett Michael A.S., Stöhr Robert, Zlotta Alexandre R., Eckstein Markus, Soorojebally Yanish, van der Schoot Deric K.E., Wullich Bernd, Burger Maximilian, Otto Wolfgang, Radvanyi François, Sirab Nanour, Pouessel Damien, van der Kwast Theo H., Hartmann Arndt, Lotan Yair, Allory Yves, Zuiverloon Tahlita C.M., van Rhijn Bas W.G.
Publisher: Elsevier Inc.
Publication year: 2022
Journal: Urologic Oncology: Seminars and Original Investigations
Journal name in source: Urologic Oncology: Seminars and Original Investigations
Volume: 40
Issue: 3
First page : 110.e1
Last page: 110.e9
eISSN: 1873-2496
DOI: https://doi.org/10.1016/j.urolonc.2021.10.010(external)
Self-archived copy’s web address: https://arts.units.it/bitstream/11368/3009211/10/3009211_1-s2.0-S1078143921004750-main-Post_print.pdf(external)
Objectives
To determine the association between the FGFR3 mutation status and immuno-histochemistry (IHC) markers (p53 and Ki-67) in invasive bladder cancer (BC), and to analyze their prognostic value in a multicenter, multi-laboratory radical cystectomy (RC) cohort.
Patients and methods
We included 1058 cN0M0, chemotherapy-naive BC patients who underwent RC with pelvic lymph-node dissection at 8 hospitals. The specimens were reviewed by uro-pathologists. Mutations in the FGFR3 gene were examined using PCR-SNaPshot; p53 and Ki-67 expression were determined by standard IHC. FGFR3 mutation status as well as p53 (cut-off>10%) and Ki-67 (cut-off>20%) expression were correlated to clinicopathological parameters and disease specific survival (DSS).
Results
pT-stage was FGFR3 mutation was associated with lower pT-stage (P<0.001), lower grade (P<0.001), pN0 (P=0.001) and prolonged DSS (P<0.001). Aberrant Ki-67 and p53 expression were associated with higher pT-stage and G3-tumors, but not with pN-stage or worse DSS, even if these IHC-biomarkers were combined (P=0.81). Significant predictors for DSS in multivariable analysis were pT-stage (HR1.5, 95%CI:1.3-1.6; P<0.001), lympho-vascular invasion (LVI) (HR1.4, 95%CI:1.2-1.7; P=0.001), pN-stage (HR1.9, 95%CI:1.6-2.4; P<0.001) and FGFR3 mutation status (HR1.6, 95%CI:1.1-2.2; P=0.011).
Conclusion
The FGFR3 mutation selectively identified patients with favorable BC at RC while p53 and Ki-67 were only associated with adverse tumor characteristics. Our results suggest that, besides tumor-stage, nodal-status and LVI, the oncogenic FGFR3 mutation may represent a valuable tool to guide adjuvant treatment and follow-up strategies after RC.
