Analysis of genetic alterations in normal bladder urothelium.
OBJECTIVE
To determine whether normal mucosa had already acquired genetic changes, we analyzed the loss of heterozygosity (LOH) and chromosomal changes in normal urothelium from patients with bladder cancer and those without any history of bladder cancer.


METHODS
Sixteen patients with bladder cancer and 15 patients with benign prostatic hyperplasia were included in this study. Tumor tissue, as well as macroscopically normal mucosa, was examined histopathologically. We performed comparative genomic hybridization according to standard protocols to detect chromosomal alterations. Furthermore, we analyzed LOH using four markers on chromosome 9 according to standard protocols for polymerase chain reaction.


RESULTS
In 75% of tumor samples, LOH or shifts were detected at least with one marker on chromosome 9. Comparative genomic hybridization revealed chromosomal alterations in 12 (75%) of 16 tumors. The loss of chromosome 9 was seen frequently (56%). LOH was observed in normal mucosa in 5 of 16 patients with tumor and 1 of 15 patients with benign prostatic hyperplasia. Chromosomal alterations were also seen in the normal mucosa of 1 patient with tumor and 2 patients with benign prostatic hyperplasia (chromosomes 1, 2, 6, 14, and 17).


CONCLUSIONS
Our results indicated that no general genetic instability is present in the bladder urothelium. Therefore, in most patients with bladder cancer, it seems that multifocality and recurrence are not caused by genetic instability of normal urothelial cells but develop owing to cell migration or intraluminal spread.
Junker
Kerstin
K
Department of Urology, Friedrich-Schiller University, Jena, Germany.
Boerner
Doreen
D
Schulze
Wolfgang
W
Utting
Michael
M
Schubert
Joerg
J
Werner
Wolfram
W
D000368:Aged; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009092:Mucous Membrane / Q000737:chemistry / Q000648:ultrastructure; D009693:Nucleic Acid Hybridization; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology; D012016:Reference Values; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology; D019459:Urothelium / Q000737:chemistry* / Q000648:ultrastructure
D004273:DNA, Neoplasm