A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer

• Published in: PloS one Vol. 7; no. 12; p. e48993
• Main Authors: Neuzillet, Yann, Paoletti, Xavier, Ouerhani, Slah, Mongiat-Artus, Pierre, Soliman, Hany, de The, Hugues, Sibony, Mathilde, Denoux, Yves, Molinie, Vincent, Herault, Aurélie, Lepage, May-Linda, Maille, Pascale, Renou, Audrey, Vordos, Dimitri, Abbou, Claude-Clément, Bakkar, Ashraf, Asselain, Bernard, Kourda, Nadia, El Gaaied, Amel, Leroy, Karen, Laplanche, Agnès, Benhamou, Simone, Lebret, Thierry, Allory, Yves, Radvanyi, François
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.12.2012; Public Library of Science (PLoS)
• Subjects: Analysis; Biochemistry; Biology; Bladder; Bladder cancer; Cancer; Development and progression; Disease Progression; Female; Fibroblast growth factor receptors; Fibroblasts; Gene Expression Regulation, Neoplastic; Genes, p53; Genetic aspects; Growth factors; Humans; Invasiveness; Life Sciences; Male; Medical Oncology - methods; Medicine; Meta-analysis; Multivariate analysis; Muscles; Mutation; p53 Protein; Pathology; Prevalence; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Studies; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumors; Urinary bladder; Urinary Bladder Neoplasms - genetics; Urine; Urology; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0048993

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of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours.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.