Multifocality of transitional cell carcinoma results from genetic instability of entire transitional epithelium.
OBJECTIVE
Multifocality of transitional cell carcinoma (TCC) has been attributed to seeding of exfoliated tumor cells or to a general sensitivity of the entire urothelium to carcinogenic stimuli. By contrast, TCC has been shown to evolve as a consequence of genetic defects and chromosomal instability. We analyzed chromosomal patterns, total DNA content, and p53 and Ki67 expression in malignant and normal transitional cells to evaluate their relationship 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 the urinary bladder and 7 of those had synchronous ureteral involvement. Two patients had ureteral TCC and a history of TCC of the bladder. Using fluorescence in situ hybridization, numerical aberrations of chromosomes 7, 9, and 17 were detected in imprint specimens of histologically verified tumor and "normal" urothelium and were compared with static ploidy and p53 and Ki67 expression.


RESULTS
Chromosome 7 was altered in 93.6%, chromosome 9 in 63.8% (including 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 aneuploid in all tumor specimens, but diploid in 20 (42.5%) of 47 normal specimens, according to lower aberration frequencies in these patients. p53 detection 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 for multifocality in the entire transitional epithelium.
Pycha
A
A
Department of Urology, University of Vienna, Austria.
Mian
C
C
Hofbauer
J
J
Brössner
C
C
Haitel
A
A
Wiener
H
H
Marberger
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology*; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics; D008297:Male; D008875:Middle Aged; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology*; D019459:Urothelium
D004273:DNA, Neoplasm; D019394:Ki-67 Antigen