Cytogenetic analysis of false-positive mucosa by photodynamic diagnosis using 5-aminolevulinic acid - possible existence of premalignant genomic alterations examined by in vitro experiment.
OBJECTIVE
Although photodynamic diagnosis is a powerful tool for the detection of flat urothelial tumors, false-positive fluorescent mucosa still requires further elucidation. Thus, we aimed to study the significance of nonmalignant fluorescent mucosa by a cytogenetic approach.


METHODS
Sixty specimens of bladder mucosa were collected from 20 patients who were suspected of having carcinoma in situ by fluorescence cystoscopy with 5-aminolevulinic acid. To detect the copy number aberrations, the multi-color fluorescence in situ hybridization technique was performed, and the variant fractions (total fractions other than those of the modal copy number) of chromosomes 7, 9 and 17 and the chromosomal instability were determined. To delineate the relevant gene to the fluorescent mucosa, a comparative genomic hybridization technique was applied for 8 established bladder cancer cell lines, and these results were compared with the in vitro fluorescent expression experiment.


RESULTS
Fluorescent mucosa was detected in 33 of the 34 malignant tissue specimens (16 carcinoma in situ, 18 other transitional cell carcinomas) and in 11 of the 26 nonmalignant tissue specimens (6 dysplasia, 20 normal mucosa), with a false-positive rate of 42.3%. The variant fraction of chromosome 9 was significantly higher in fluorescent than in non-fluorescent mucosa, not only for all tissues (33 vs. 17%; p = 0.0069), but also for nonmalignant tissues (28 vs. 15%; p = 0.0225). There was no alteration in chromosome 9 in 1 cell line without fluorescent mucosa, while 5 of the 7 cell lines with fluorescent mucosa had a common deleted region on 9q24.1.


CONCLUSIONS
These data suggest that a substantial portion of nonmalignant fluorescent mucosa harbors alterations in chromosome 9.
Matsuyama
Hideyasu
H
Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan. hidde@yamaguchi-u.ac.jp
Yamamoto
Yoshiaki
Y
Nagao
Kazuhiro
K
Ohmi
Chietaka
C
Sakano
Shigeru
S
Sasaki
Kohsuke
K
D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D002278:Carcinoma in Situ / Q000188:drug therapy / Q000235:genetics; D002869:Chromosome Aberrations; D003582:Cytogenetics / Q000379:methods*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D013050:Spectrometry, Fluorescence / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics*
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid