Prevalence and prognostic significance of microsatellite alterations in young patients with bladder cancer

Abstract

Mutations in microsatellite sequences are a hallmark of neoplastic transformation and have been reported in the majority of human cancers. Conflicting results have been reported on the role of microsatellite alterations in bladder tumorigenesis and it has been suggested that they might be mainly involved in the development of bladder cancers in young patients. In this study, DNA was extracted from laser-microdissected samples of 51 superficial papillary bladder urothelial carcinomas arising in young patients and was analyzed for the status of 19 microsatellite loci previously reported to be associated with bladder tumorigenesis. The occurrence and the pattern of microsatellite alterations, in form of loss or length variation, was evaluated and correlated with other clinicopathologic and molecular markers. The prognostic significance of these alterations was also evaluated. Loss of heterozygosity at one or more loci was detected in all 51 tumors analyzed. Length variation in at least one locus was observed in 48 (94%) of the cases. The microsatellite that was more frequently altered was D11S488 (69%), followed by D9S162 (61%), D3S3050 (55%), D3S1300 (51%) and D4S243 (51%), all the remaining being altered in less than 50% of cases. The occurrence of microsatellite alterations was not associated with tumor grade nor with tumor stage, the expression of p53, cyclin D1 or the cyclin-dependent kinase-inhibitor p27Kip1 while it was significantly more frequent in tumors with increased expression of the proliferation marker MIB-1 (P ¼ 0.003). The occurrence of alterations at the analyzed loci was associated with a reduced risk of tumor recurrence (P ¼ 0.04 by log-rank test) and disease progression (P ¼ 0.02) in a univariate analysis. These findings demonstrate that microsatellite alterations are frequent and early events and might have a prognostic significance in bladder cancers arising at young age.

Urothelial neoplasms in pediatric and young adult patients: A large single-center series

“…A number of studies have examined the role of microsatellite instability in the pathogenesis of urothelial neoplasms in young patients. These studies have reported conflicting results though, with some showing significant microsatellite instability [3, 23] and others showing minimal microsatellite instability [6, 7]. The collected findings of these studies suggest a role for additional research into the unique genetic mechanisms associated with urothelial neoplasms in young patients.…”

Urothelial Neoplasms of the Urinary Bladder Occurring in Young Adult and Pediatric Patients

“…Both contradicted 2 earlier studies which reported high MSI (100%) in bladder cancer from patients aged 35 to 55 years 34 and frequent microsatellite alterations (100%) in superficial bladder urothelial carcinomas from patients aged 20 to 45 years. 33 It was suggested that use of large number (22 panels) of dinucleotide markers may possibly explain the higher MSI detected. [32][33][34] Of note, the patient cohorts in those 2 studies were much older than in the study by Wild et al 31 (4 to 19 y) and also had higher number of invasive and grade 3 tumors.…”

“…33 It was suggested that use of large number (22 panels) of dinucleotide markers may possibly explain the higher MSI detected. [32][33][34] Of note, the patient cohorts in those 2 studies were much older than in the study by Wild et al 31 (4 to 19 y) and also had higher number of invasive and grade 3 tumors. The study by Migaldi et al 33 showed microsatellite alteration to be associated with reduced risk of tumor recurrence and disease progression, but this was only shown in the univariate analysis.…”

“…4,13,29,30 Similarly, observations about the genetic and molecular make-up of bladder urothelial neoplasms in young patients have varied. [31][32][33][34][35] One reason for this variability is the differing criteria to define "young" patients in published series which have used cut-offs of 20, 30, or 40 to 45 years of age. 3,4,6,13,[26][27][28][29][30][31][32][33][34][35] Owing to conflicting opinions, currently there are no current standardized recommendations in terms of diagnostic approach and management specific for young or pediatric patients with bladder urothelial neoplasms.…”

Incidental Finding of Urothelial Cell Carcinoma in a Young Patient During an Early Obstetrical Sonogram

“…1 Young patients tend to present more frequently with noninvasive low-grade tumors, as in this case being presented. 2,3 Case Report A 17-year-old female, gravida 1, para 0, presented to the emergency room with low back pain and spotting in her first trimester. An early obstetrical sonogram was ordered to evaluate the pregnancy.…”