Multifocality of transitional cell carcinoma results from genetic instability of entire transitional epithelium

Objectives, Multifocality of transitional cell carcinoma (TCC) has been att ributed to seeding of exfoliated tumor cells or to a general sensitivity of the entire urothelium to carcinogenic stimuli. By contrast, TCC has been s hown to evolve as a consequence of genetic defects and chromosomal instabil ity. We analyzed chromosomal patterns, total DNA content, and p53 and Ki67 expression in malignant and normal transitional cells to evaluate their rel ationship to the development of multifocal TCC, Methods. included in the study were 47 patients, 16 women and 31 men, with a mean age of 70.04 years (range 37 to 83). Of 47 patients, 45 had TCC of t he urinary bladder and 7 of those had synchronous ureteral involvement. Two patients had ureteral TCC and a history of TCC of the bladder. Using fluor escence in situ hybridization, numerical aberrations of chromosomes 7, 9, a nd 17 were detected in imprint specimens of histologically verified tumor a nd "normal" urothelium and were compared with static ploidy and p53 and Ki6 7 expression. Results. Chromosome 7 was altered in 93.6%, chromosome 9 in 63.8% (includin g monosomy), and chromosome 17 in 87.2% of the 47 analyzed tumor and normal imprints. Differences between tumor and normal epithelium were observed in aberrational frequencies (number of cells showing chromosomal aberrations calculated on 200 cells counted, given in percentages). DNA content was ane uploid in all tumor specimens, but diploid in 20 (42.5%) of 47 normal speci mens, according to lower aberration frequencies in these patients. p53 dete ction was positive in 82.9% of the tumor specimens and 76.6% of the normal specimens. Ki67 was positive in 87.2% of the tumor imprints and in 72.3% of the normal specimens. Conclusions. These data suggest a general genetic instability as a reason f or multifocality in the entire transitional epithelium. UROLOGY 53: 92-97, 1999. (C) 1999, Elsevier Science Inc, AII rights reserved.