Chromosomal aneuploidies in bladder cancer, chronic cystitis and normal urothelium detected by fluorescence in situ hybridization

Abstract

The objective of present work is to investigate the occurrence of numerical alterations in lesions and bladder carcinomas that may be helpful in early diagnosis. Fluorescence in situ hybridization (FISH) was applied to identify such alterations in chromosomes 7, 9 and 17, in interphase nuclei of 14 fresh bladder tumor specimens (13 transitional cell carcinomas, TCC, and 1 undifferentiated anaplasic carcinoma, UAC), and 5 specimens derived from the TCC patients (2 chronic cystitis, UCC, and 3 macroscopically normal urothelium biopsies, MNU). The most frequent anomalies in malignant tumors of the bladder were trisomy /tetrasomy 7 (6/14=43%), trisomy/tetrasomy 17 (7/14=50%) and monosomy 9 (4/14=29%). The two chronic cystitis samples showed monosomy 9, whereas one macroscopically normal urothelium sample presented similar findings (polysomy 7, 9, and 17) observed in the matched tumoral tissue. Two carcinomas, an invasive grade IV (TCC13) and an invasive primary (UAC14), presented trisomy/tetrasomy 7, 9 and 17 suggesting that the cells were polyploidy. These results strengthens the involvement of chromosomes 7, 9, and 17 in urothelial carcinogenesis. The alterations of chromosomes 7 and 9 are related to the initiation process; and of chromosome 17, to tumoral progression and recurrence. Moreover, the results also support the hypothesis that chronic cystitis and normal urothelium from patients with bladder carcinoma can carry important chromosome abnormalities which may predict risk for tumor progression and recurrence. Thus, interphase FISH may be a useful tool for early diagnosis in patients at risk of disease and for follow-up in cases of recurrence and metastase.