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. 2010 May;183(5):1738-43.
doi: 10.1016/j.juro.2009.12.105. Epub 2010 Mar 17.

Loss of heterozygosis on IFN-alpha locus is a prognostic indicator of bacillus Calmette-Guerin response for nonmuscle invasive bladder cancer

Tommaso Cai  1 , Gabriella Nesi, Maurizio Dal Canto, Galliano Tinacci, Nicola Mondaini, Mauro Piazzini, Pierangelo Geppetti, Riccardo Bartoletti
Affiliations

Loss of heterozygosis on IFN-alpha locus is a prognostic indicator of bacillus Calmette-Guerin response for nonmuscle invasive bladder cancer

Tommaso Cai et al. J Urol. 2010 May.

Abstract

Purpose: We evaluated the role of loss of heterozygosity on the interferon-alpha locus to predict the response to bacillus Calmette-Guerin therapy in patients with nonmuscle invasive bladder cancer.

Materials and methods: A total of 117 consecutive patients were selected, including 77 with nonmuscle invasive bladder cancer and 40 controls. Loss of heterozygosity on the interferon-alpha locus (chromosome 9p21) was assessed in blood and urine samples before transurethral resection. All patients underwent transurethral resection and then 6 weekly bacillus Calmette-Guerin instillations. Those with nonmuscle invasive bladder cancer were assigned to groups 1 and 2 with and without loss of heterozygosity on the interferon-alpha locus, respectively.

Results: Of the 77 patients with nonmuscle invasive bladder cancer 39 (50.6%) had loss of heterozygosity on the interferon-alpha locus (group 1) and 38 (49.4%) had no alteration (group 2). Only 1 of 40 controls showed loss of heterozygosity on the interferon-alpha locus. At the end of followup 13 patients in group 1 and 27 in group 2 were alive without recurrence. We noted a significant difference between loss of heterozygosity on interferon-alpha and followup status (dF 01, LR 11.252, p = 0.003). Kaplan-Meier analysis revealed a significant difference in recurrence probability (response to bacillus Calmette-Guerin) and loss of heterozygosity on interferon-alpha (p <0.0001). On multivariate analysis loss of heterozygosity (HR 4.09, 95% CI 2.59-6.28, p = 0.002), grade (grade 3 HR 3.31, 95% CI 1.38-3.35, p = 0.03) and the number of lesions (3 or greater HR 2.31, 95% CI 1.38-3.25, p = 0.03) were independent predictors of the bacillus Calmette-Guerin response.

Conclusions: This study highlights the predictive value of loss of heterozygosity analysis on interferon-alpha in patients with nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin.

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