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Tumor heterogeneity of fibroblast growth factor receptor 3 (FGFR3) mutations in invasive bladder cancer: implications for perioperative anti-FGFR3 treatment.


ABSTRACT:

Background

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.

Patients and methods

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).

Results

We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ?T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ?T2-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.

Conclusions

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.

SUBMITTER: Pouessel D 

PROVIDER: S-EPMC6608613 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Tumor heterogeneity of fibroblast growth factor receptor 3 (FGFR3) mutations in invasive bladder cancer: implications for perioperative anti-FGFR3 treatment.

Pouessel D D   Neuzillet Y Y   Mertens L S LS   van der Heijden M S MS   de Jong J J   Sanders J J   Peters D D   Leroy K K   Manceau A A   Maille P P   Soyeux P P   Moktefi A A   Semprez F F   Vordos D D   de la Taille A A   Hurst C D CD   Tomlinson D C DC   Harnden P P   Bostrom P J PJ   Mirtti T T   Horenblas S S   Loriot Y Y   Houédé N N   Chevreau C C   Beuzeboc P P   Shariat S F SF   Sagalowsky A I AI   Ashfaq R R   Burger M M   Jewett M A S MA   Zlotta A R AR   Broeks A A   Bapat B B   Knowles M A MA   Lotan Y Y   van der Kwast T H TH   Culine S S   Allory Y Y   van Rhijn B W G BW  

Annals of oncology : official journal of the European Society for Medical Oncology 20160418 7


<h4>Background</h4>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.<h4>Patients and methods</h4  ...[more]

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