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

Sarah Lott, Mingsheng Wang, Shaobo Zhang, Gregory T. MacLennan, Antonio Lopez-Beltran, Rodolfo Montironi, Ming Tse Sung, Puay Hoon Tan, Liang Cheng

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)627-632
Number of pages6
JournalModern Pathology
Volume22
Issue number5
DOIs
StatePublished - May 1 2009

Keywords

  • Fibroblast growth factor receptor 3
  • Inverted papilloma
  • TP mutations
  • Tumorigenesis
  • Urinary bladder
  • Urinary tract

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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