Chromosome 9 deletions and recurrence of superficial bladder cancer: identification of four regions of prognostic interest

Abstract

In a previous study, loss of heterozygosity (LOH) of 28 chromosome 9 microsatellite markers was assessed on 139 Ta/T1 bladder tumors. LOH at one or more loci was detected in 67 tumors, 62 presenting subchromosomal deletions. One hundred and thirty-three of these patients have now been followed for up to 8 years. The purpose of the present study was to evaluate the potential biological significance of chromosome 9 deletions in superficial bladder tumors at initial diagnosis. High grade was associated with LOH (P=0.004). Large tumors carried more frequently 9p deletions (P=0.022). Female patients had more chromosome 9q LOH than male patients did (P=0.010). Chromosome 9 LOH at all loci was associated with an elevated risk of recurrence but four regions were associated with a particularly high risk of recurrence. Multivariate analysis taking into account grade, stage, size and number of tumors showed that tumors deleted in the regions 9ptr-p22, 9q22.3, 9q33, and 9q34 recurred significantly more rapidly than those without deletions (Recurrence rate ratio=2.32, 2.53, 2.52 and 2.43 respectively). Log-rank statistics comparing Kaplan-Meier survival curves for the same chromosomal regions confirmed the correlation (P=0.0002, 0.010, 0.002 and 0.009 respectively). Only four patients progressed to muscle-invasive disease. They all had extensive deletions on 9q but none had deletions at 9ptr-p22. This study suggests a link between chromosome 9 anomalies and recurrence of superficial bladder cancer.