A1 Refereed original research article in a scientific journal
Tumor heterogeneity of fibroblast growth factor receptor 3 (FGFR3) mutations in invasive bladder cancer: implications for perioperative anti-FGFR3 treatment
Authors: Pouessel D, Neuzillet Y, Mertens LS, van der Heijden MS, de Jong J, Sanders J, Peters D, Leroy K, Manceau A, Maille P, Soyeux P, Moktefi A, Semprez F, Vordos D, de la Taille A, Hurst CD, Tomlinson DC, Harnden P, Bostrom PJ, Mirtti T, Horenblas S, Loriot Y, Houede N, Chevreau C, Beuzeboc P, Shariat SF, Sagalowsky AI, Ashfaq R, Burger M, Jewett MAS, Zlotta AR, Broeks A, Bapat B, Knowles MA, Lotan Y, van der Kwast TH, Culine S, Allory Y, van Rhijn BWG
Publisher: OXFORD UNIV PRESS
Publication year: 2016
Journal: Annals of Oncology
Journal name in source: ANNALS OF ONCOLOGY
Journal acronym: ANN ONCOL
Volume: 27
Issue: 7
First page : 1311
Last page: 1316
Number of pages: 6
ISSN: 0923-7534
eISSN: 1569-8041
DOI: https://doi.org/10.1093/annonc/mdw170
Fibroblast growth factor receptor 3 (FGFR3) is a major potential actionable target in urothelial bladder cancer (BC). We found that FGFR3 mutations appeared conserved in primary BC and corresponding lymph-node metastases. We also showed that the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. This suggests that personalized anti-FGFR3 therapy may improve BC treatment in the perioperative setting.Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated >FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response.We evaluated possible >FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, >n = 61) and in radical cystectomy (RC, >n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, >n = 201).We found ZFGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) a parts per thousand yenT2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight >FGFR3 mutant a parts per thousand yenT2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) >FGFR3 mutations in RC specimens. >FGFR3 mutation was associated with pN0 (>P < 0.001) at RC. In 10/201 (5%) LN+, an >FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type.>FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.
