A Meta-Analysis of the Relationship between <em>FGFR3</em> and <em>TP53</em> Mutations in Bladder Cancer

<div><p><em>TP53</em> and <em>FGFR3</em> mutations are the most common mutations in bladder cancers. <em>FGFR3</em> mutations are most frequent in low-grade low-stage tumours, whereas <em>TP53</em> mutations are most frequent in high-grade high-stage tumours. Several studies have reported <em>FGFR3</em> and <em>TP53</em> mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for <em>FGFR3</em> and <em>TP53</em> mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. <em>TP53</em> and <em>FGFR3</em> mutations were not independent events for all tumours considered together (OR = 0.25 [0.18–0.37], <em>p</em> = 0.0001) or for pT1 tumours alone (OR = 0.47 [0.28–0.79], <em>p</em> = 0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, <em>FGFR3</em> and <em>TP53</em> mutations were independent events (OR = 0.56 [0.23–1.36] (<em>p</em> = 0.12) and OR = 0.99 [0.37–2.7] (<em>p</em> = 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 <em>CIS</em> pathway, in which <em>FGFR3</em> mutations are rare, and the Ta pathway, in which <em>FGFR3</em> mutations are frequent. <em>TP53</em> mutations occur at the earliest stage of the <em>CIS</em> pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.</p>