title: Genomic aberrations are rare in urothelial neoplasms of patients 19 years or younger.
abstract: Urothelial neoplasms in patients 19 years of age or younger are rare, and the data regarding clinical outcome are conflicting. Molecular data are not available. Urothelial tumours from 14 patients aged 4 to 19 years were analysed, including FGFR3 and TP53 mutation screening, comparative genomic hybridization (CGH), UroVysion FISH analysis, polymerase chain reaction for human papillomavirus (HPV), microsatellite analysis using the NIH consensus panel for detection of microsatellite instability (MSI) and six markers for loss of heterozygosity on chromosome arms 9p, 9q, and 17p and immunohistochemistry for TP53, Ki-67, CK20 and the mismatch repair proteins (MRPs) hMSH2, hMLH1, and hMSH6. Based on the 2004 WHO classification, one urothelial papilloma, seven papillary urothelial neoplasms of low malignant potential (PUNLMPs), five low-grade, and one high-grade papillary urothelial carcinoma were included. No multifocal tumours were found and recurrence was seen in only one patient with a urothelial papilloma. All patients were alive with no evidence of disease at a median follow-up of 3.0 years. We found no mutations in FGFR3, deletions of chromosome arms 9p, 9q or 17p, MSI or MRP loss, or HPV positivity in any of the patients. Three cases showed chromosome alterations in CGH analyses, urothelial dedifferentiation with CK20 overexpression, or aneuploidy, and one TP53 mutation with TP53 overexpression was found. Urothelial neoplasms in people younger than 20 years are predominantly low grade and are associated with a favourable clinical outcome. Genetic alterations frequently seen in older adults are extremely rare in young patients. Urothelial neoplasms in children and young adults appear to be biologically distinct and lack genetic instability in most cases.
authors.affiliation: Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: P J
authors.initials: PJ
authors.lastname: Wild
authors.forename: J
authors.initials: J
authors.lastname: Giedl
authors.forename: R
authors.initials: R
authors.lastname: Stoehr
authors.forename: K
authors.initials: K
authors.lastname: Junker
authors.forename: S
authors.initials: S
authors.lastname: Boehm
authors.forename: J M M
authors.initials: JM
authors.lastname: van Oers
authors.forename: E C
authors.initials: EC
authors.lastname: Zwarthoff
authors.forename: H
authors.initials: H
authors.lastname: Blaszyk
authors.forename: S W
authors.initials: SW
authors.lastname: Fine
authors.forename: P A
authors.initials: PA
authors.lastname: Humphrey
authors.forename: L P
authors.initials: LP
authors.lastname: Dehner
authors.forename: M B
authors.initials: MB
authors.lastname: Amin
authors.forename: J I
authors.initials: JI
authors.lastname: Epstein
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D000293:Adolescent; D000328:Adult; D052685:Alphapapillomavirus / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D020411:Oligonucleotide Array Sequence Analysis; D010212:Papilloma / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology; D019459:Urothelium
chemical_list: D004279:DNA, Viral; D051498:Receptor, Fibroblast Growth Factor, Type 3