FGFR3 and TP53 mutation analysis in inverted urothelial papilloma: Incidence and etiological considerations

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Modern Pathology (Impact Factor: 6.19). 03/2009; 22(5):627-632. DOI: 10.1038/modpathol.2009.28


Urothelial papillomas and low-grade urothelial carcinomas have shown a high incidence of fibroblast growth factor receptor 3 (FGFR3) mutations and are associated with a favorable prognosis. The association of FGFR3 mutations with inverted papillomas is less known. We analyzed 20 cases of inverted papilloma in the urinary tract. Mutations of FGFR3 (exons 7, 10, and 15) and TP53 genes were evaluated by DNA sequencing in these cases. Point mutations of the FGFR3 gene were identified in 45% (9 of 20) of inverted papillomas with four cases exhibiting mutations at multiple exons. Seven cases had exon 7 mutations containing R248C, S249T, L259L, P260P, and V266M. Two cases had exon 10 and 15 mutations including A366D, H412H, E627D, D641N, and H643D; five cases had N653H. The most frequent mutation was identified at R248C. None of the inverted papillomas exhibited mutations in TP53. During a mean follow-up of 78 months, none had recurrence or developed urothelial carcinoma. These findings support the concept that low-grade and low-stage urothelial neoplasms arise in a background of molecular changes that are distinctly different from the molecular changes of high-grade and high-stage urothelial cancers.Keywords: urinary bladder, urinary tract, inverted papilloma, fibroblast growth factor receptor 3, tumorigenesis, TP mutations

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Available from: Liang Cheng, Mar 26, 2014
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    • "Follow up studies in inverted papilloma does not suggest a significantly increased risk of urothelial carcinoma, and its synchronous occurrence with urothelial carcinoma is rare.9–18 Generally, different pathways of tumorigenesis are thought to be involved in these two lesions.18 "
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    • "However, this statement has been challenged because in rare cases, IUPs coexist with malignant urothelial neoplasms (Cheville et al. 2000). Molecular analyses also confirmed that IUPs arise on the basis of genetic changes, which are strikingly different from those of high-grade/high-stage urothelial neoplasms (Sung et al. 2006a; Lott et al. 2009). Therefore, distinction between IUP and inverted growth pattern of LG-UCC is essential. "
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