Molecular characteristics of urothelial neoplasms in children and young adults: a subset of tumors from young patients harbors chromosomal abnormalities but not FGFR3 or TP53 gene mutations

Abstract

Urothelial neoplasms in children and young adult patients are rare and hypothesized to have a lower rate of recurrence and progression than those of older adults. Because of their rarity, data regarding molecular abnormalities in these tumors are limited. We studied molecular characteristics of urothelial neoplasms from patients under age 30 years using UroVysion fluorescence in situ hybridization (chromosomes 3, 7, 17, and 9p21) and DNA mutational analysis for the FGFR3 and TP53 genes. Seventeen tumors were identified in patients 6–26 years of age, including low-grade papillary urothelial carcinoma (n=10), high-grade papillary urothelial carcinoma (n=5), urothelial papilloma (n=1), and papillary urothelial neoplasm of low malignant potential (n=1). No tumor demonstrated mutation of FGFR3 or TP53. Chromosomal abnormalities were detected only in patients aged ≥19 years: two low-grade urothelial carcinomas had loss of 9p21 as a sole chromosomal abnormality and three high-grade urothelial carcinomas had other or multiple chromosomal abnormalities. Under age 19 years, no tumor showed molecular abnormalities with either method (five low-grade papillary urothelial carcinomas and one each of high-grade papillary urothelial carcinoma, papillary urothelial neoplasm of low malignant potential, and urothelial papilloma). Our results support the idea that mutations of the FGFR3 and TP53 genes are rare or absent in urothelial neoplasms of young patients. In contrast, chromosomal abnormalities detected by UroVysion fluorescence in situ hybridization are sometimes present in patients above 19–20 years of age. This finding supports the recently proposed hypothesis that an age of 19–20 years separates distinct molecular pathways of urothelial carcinogenesis.