Prognostic value of loss of heterozygosity at chromosome 9p in non-muscle-invasive bladder cancer

Abstract

Objective: To investigate the prognostic value of loss of heterozygosity (LOH) at chromosome 9p in patients with non-muscle-invasive bladder cancer (NMI-BC).

Methods: Between 2000 and 2006, we included in the study 84 patients with NMI-BC. LOH analyses were performed on tumor tissue using 3 microsatellite markers at chromosome 9p. Associations of LOH with recurrence and progression of the tumors were evaluated.

Results: Frequency of LOH at 9p was 11.1%, 29.0%, and 31.6% in pTaG1, pTaG2, and pT1G3 tumors, respectively. Recurrence occurred in 27 patients. None of the markers was able to predict recurrence. Progression occurred in 9.5% of the cases, with progression to muscle-invasive bladder cancer (MI-BC) in 4.8% of the cases. LOH at IFN-alpha was significantly associated with progression to MI-BC (P = .006). In the case of LOH at IFN-alpha, 2-year progression-free survival and progression-free survival to MI-BC were both 59.3%, compared with 97.1% and 98.6%, respectively, in case of conservation of LOH in multivariable analysis, LOH at IFN-alpha remained statistically associated with progression and progression to MI-BC. LOH at IFN-alpha was a significant and independent predicting factor of progression and progression to MI-BC, with P = .05 and 0.01 (HR 4.8 for progression; HR 24.2 for muscle invasion).

Conclusions: Our study suggests that LOH at IFN-alpha is an independent prognostic factor for progression to MI-BC. LOH analysis of bladder tumors may help in the management of NMI-BC. Specifically, it could be of use in selecting patients for early aggressive treatment and/or in planning close follow-up schedule.