Molecular genetic alterations in the laser-capture-microdissected stroma adjacent to bladder carcinoma.
BACKGROUND
Urothelial carcinoma commonly manifested loss of heterozygosity (LOH) at different regions of chromosomes 17p, 3p, and 9q. Recent studies suggested that bladder stromal cells may be implicated in the growth and progression of urothelial carcinoma. To better understand the genetic alterations in the stromal cells in patients with bladder carcinoma, the authors evaluated the prevalence of allelic loss at three microsatellite polymorphic markers on chromosomes 17p13 (TP53), 3p25-26 (D3S3050), and 9q32-33 (D9S177). In addition, the pattern of X-chromosome inactivation of the stromal cells was evaluated by analyzing the DNA methylation pattern at a polymorphic site on the androgen receptor gene.


METHODS
The authors studied 18 female patients who underwent either transurethral resection (n = 2) or radical cystectomy (n = 16) for high-grade muscle-invasive urothelial carcinoma of the urinary bladder. Genomic DNA samples from the stromal cells immediately adjacent to the tumor and the tumor itself were prepared from formalin-fixed, paraffin-processed tissues using laser-assisted microdissection and LOH was determined.


RESULTS
The stromal cells showed a high frequency of LOH on chromosomes 17p13 (29%), 3p25-26 (61%), and 9q32-33 (47%) with no clear concordance with the adjacent tumor cells. Fourteen specimens (78%) showed LOH in the stroma in at least 1 of 3 markers examined. Nonrandom X-chromosome inactivation was frequent in the stromal cells (50% of informative specimens).


CONCLUSIONS
The current study revealed that some of the genetic changes that commonly occur with invasive urothelial carcinoma were frequently found in the adjacent stroma and suggested that the stroma of urothelial carcinoma may play an important role in bladder carcinogenesis.
Department of Urology, Indiana University School of Medicine, Indianapolis, Indianapolis 46202, USA.
Ryan F
RF
Paterson
Thomas M
TM
Ulbright
Gregory T
GT
MacLennan
Shaobo
S
Zhang
Chong-Xian
CX
Pan
Christopher J
CJ
Sweeney
Curtiss R
CR
Moore
Richard S
RS
Foster
Michael O
MO
Koch
John N
JN
Eble
Liang
L
Cheng
D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D004210:Dissection; D005260:Female; D006801:Humans; D007834:Lasers; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009361:Neoplasm Invasiveness; D017154:Stromal Cells; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology