title: A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.
abstract: TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18-0.37], p = 0.0001) or for pT1 tumours alone (OR = 0.47 [0.28-0.79], p = 0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23-1.36] (p = 0.12) and OR = 0.99 [0.37-2.7] (p = 0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.
authors.affiliation: Department of Urology, Hôpital Foch, Université de Versailles - Saint-Quentin-en-Yvelines, Suresnes, France.
authors.forename: Yann
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authors.lastname: Neuzillet
authors.forename: Xavier
authors.initials: X
authors.lastname: Paoletti
authors.forename: Slah
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authors.lastname: Ouerhani
authors.forename: Pierre
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authors.lastname: Mongiat-Artus
authors.forename: Hany
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authors.lastname: Soliman
authors.forename: Hugues
authors.initials: H
authors.lastname: de The
authors.forename: Mathilde
authors.initials: M
authors.lastname: Sibony
authors.forename: Yves
authors.initials: Y
authors.lastname: Denoux
authors.forename: Vincent
authors.initials: V
authors.lastname: Molinie
authors.forename: Aurélie
authors.initials: A
authors.lastname: Herault
authors.forename: May-Linda
authors.initials: ML
authors.lastname: Lepage
authors.forename: Pascale
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authors.lastname: Maille
authors.forename: Audrey
authors.initials: A
authors.lastname: Renou
authors.forename: Dimitri
authors.initials: D
authors.lastname: Vordos
authors.forename: Claude-Clément
authors.initials: CC
authors.lastname: Abbou
authors.forename: Ashraf
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authors.lastname: Bakkar
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.forename: Nadia
authors.initials: N
authors.lastname: Kourda
authors.forename: Amel
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authors.lastname: El Gaaied
authors.forename: Karen
authors.initials: K
authors.lastname: Leroy
authors.forename: Agnès
authors.initials: A
authors.lastname: Laplanche
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
authors.forename: Thierry
authors.initials: T
authors.lastname: Lebret
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.forename: François
authors.initials: F
authors.lastname: Radvanyi
mesh_terms: D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008297:Male; D008495:Medical Oncology / Q000379:methods; D009154:Mutation; D015995:Prevalence; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3