Introduction/Objective: N-acetyltransferase 2 (NAT2), mapped to 8p22, is a polymorphic enzyme which metabolizes aromatic amines. Loss of heterozygosity of 8p22 is associated with an increased risk of bladder cancer. This study evaluated NAT2 and chromosome 8 in sequential tumours from bladder cancer patients to determine if NAT2 alterations increase the risk of progression. Materials and Methods: Thirty-seven sequential carcinomas from 19 patients were assessed using fluorescence in situ hybridization. Results: Five carcinomas showed loss of NAT2; 4 of these were from pTa/pT1 tumours. Polysomy 8 was observed in 4 of 14 (29%) primary carcinomas (pTa/pT1), in 4 of 12 (33%) pTa/pT1 recurrences, and in 90% (9/10) of the detrusor muscle invasive tumours (pT2+). 6 of 8 (75%) locally invasive tumours with polysomy 8 were from patients who subsequently developed disease progression (pT2+). In total, 13.5% (5/37) of the carcinomas were abnormal for NAT2, and 46% (17/37) were abnormal for chromosome 8 copy number. Polysomy 8 was associated with high grade (p = 0.01) and stage (p = 0.03) and disease progression (p = 0.03). Conclusion: Whilst there does not appear to be an association between loss of NAT2 and risk of progression in transitional cell carcinoma, the high rate of polysomy of chromosome 8 implies that other genes on this chromosome significantly influence disease progression.

Keywords:
Bladder cancer, Chromosome 8, N-acetyltransferase 2, Fluorescence in situ hybridization, Recurrence/progression, bladder cancer
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© 2001 S. Karger AG, Basel
2001
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