Detection of chromosomal instability in preneoplastic flat lesions and conditions of the urinary bladder using UroVysion fluorescence in-situ hybridization

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Abstract

Purpose

Identification of genetic alterations in preneoplastic lesions to frank cancer helps in elucidating the progression of these genetic changes. The aim of the present study was to identify chromosomal imbalance using UroVysion fluorescence in-situ hybridization in patients with various preneoplastic flat lesions and conditions in routine paraffin-embedded bladder biopsy samples.

Materials and methods

A total of148 paraffin-embedded tissue blocks from 75 patients with preneoplastic flat lesions and conditions [hyperplasia, reactive atypia, dysplasia, carcinoma in situ (CIS), squamous metaplasia, intestinal metaplasia, and control] were analyzed using tissue sections hybridized with centromeric probes for chromosomes 3, 7, and 17 and a locus-specific probe 9p21 for detecting cytogenetic abnormalities.

Results

Polysomy of at least one of the chromosomes was found in more than 90% of samples in CIS and invasive bladder tumors, whereas it was found in 80% of samples in dysplasia. The mean percentage of polysomic cells in flat urothelial hyperplasia, reactive urothelial atypia, intestinal metaplasia, keratinizing squamous metaplasia, and histologically normal urothelium in patients with tumors ranged from 11 to 20%, whereas in CIS and dysplasia it was 69 and 49%, respectively. Deletion of the P16 locus was most frequently observed in aneuploid lesions.

Conclusion

Detection of chromosomal imbalance with UroVysion fluorescence in-situ hybridization is a useful method for the detection of genetically unstable preneoplastic flat lesions and conditions, and can help in resolving difficult cases, particularly in the differential diagnosis of reactive atypia and dysplasia. Moreover, evaluation of ongoing genetic instability might provide additional insight into urinary bladder cancer risk assessment beyond that of the location and histology of the premalignant lesion.

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