| Added by | celine.gongora |
|---|---|
| Group name | EquipeCG |
| Item Type | Journal Article |
| Title | Tumor heterogeneity of fibroblast growth factor receptor 3 (FGFR3) mutations in invasive bladder cancer: implications for perioperative anti-FGFR3 treatment |
| Creator | Pouessel et al. |
| Author | D. Pouessel |
| Author | Y. Neuzillet |
| Author | L. S. Mertens |
| Author | M. S. van der Heijden |
| Author | J. de Jong |
| Author | J. Sanders |
| Author | D. Peters |
| Author | K. Leroy |
| Author | A. Manceau |
| Author | P. Maille |
| Author | P. Soyeux |
| Author | A. Moktefi |
| Author | F. Semprez |
| Author | D. Vordos |
| Author | A. de la Taille |
| Author | C. D. Hurst |
| Author | D. C. Tomlinson |
| Author | P. Harnden |
| Author | P. J. Bostrom |
| Author | T. Mirtti |
| Author | S. Horenblas |
| Author | Y. Loriot |
| Author | C. Chevreau |
| Author | P. Beuzeboc |
| Author | S. F. Shariat |
| Author | A. I. Sagalowsky |
| Author | R. Ashfaq |
| Author | M. Burger |
| Author | M. a. S. Jewett |
| Author | A. R. Zlotta |
| Author | A. Broeks |
| Author | B. Bapat |
| Author | M. A. Knowles |
| Author | Y. Lotan |
| Author | T. H. van der Kwast |
| Author | S. Culine |
| Author | Y. Allory |
| Author | B. W. G. van Rhijn |
| 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. |
| Publication | Annals of Oncology: Official Journal of the European Society for Medical Oncology |
| Volume | 27 |
| Issue | 7 |
| Pages | 1311-1316 |
| Date | 07 2016 |
| Journal Abbr | Ann. Oncol. |
| Language | eng |
| DOI | 10.1093/annonc/mdw170 |
| ISSN | 1569-8041 |
| Short Title | Tumor heterogeneity of fibroblast growth factor receptor 3 (FGFR3) mutations in invasive bladder cancer |
| Library Catalog | PubMed |
| Extra | PMID: 27091807 |
| Tags | Adult, AFU, Aged, Biomarkers, Tumor, bladder, cancer, clinic, Clinical Decision-Making, Cystectomy, Female, FGFR3, Gene Expression Regulation, Neoplastic, Genetic Heterogeneity, Humans, Lymph Nodes, Male, Middle Aged, Mutation, mutations, Perioperative Period, Receptor, Fibroblast Growth Factor, Type 3, targeted therapy, Urinary Bladder Neoplasms |
| Date Added | 2019/05/14 - 18:23:24 |
| Date Modified | 2019/10/24 - 17:28:52 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
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