Loss of heterozygosity on chromosome 5p13-12 predicts adverse prognosis in advanced bladder cancer independent of tumor stage and grade.
OBJECTIVE
The individual prognosis in patients with bladder cancer is only partially predicted by tumor stage and grade. Various molecular markers have been shown to correlate with disease progression and prognosis but few add some predictive capacity beyond that offered by standard clinical and pathological parameters.


METHODS
A total of 191 urothelial carcinomas from 157 patients were analyzed. Paired normal and tumor cells were microdissected by manual and microbeam-microdissection of membrane mounted native tissue, and analyzed for loss of heterozygosity (LOH) at a critical region of LOH on chromosome 5p13-12 that is involved in bladder cancer progression. LOH data were correlated with progression-free and tumor specific survival by multivariate analysis.


RESULTS
Informativity of the assay was 60.7%. Log rank analysis of 100 evaluable patients showed a progression-free survival benefit without LOH at 5p13-12 of more than 3 years (p <0.01). Mean followup was 36 months. Multivariate analysis revealed that this benefit was not predicted by tumor stage and grade alone in advanced disease (stages T3/4 and/or N+/M+, stages III/IV).


CONCLUSIONS
LOH at the critical region on chromosome 5p13-12 is a molecular marker of adverse prognosis in advanced bladder carcinoma independent of tumor stage and grade.
Böhm
Malte
M
Department of Urology, Institute of Human Genetics, Ott-von-Guericke University, Magdeburg, Germany.
Wieland
Ilse
I
Schmidt
Claus
C
Rubben
Herbert
H
Allhoff
Ernst Peter
EP
D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D018450:Disease Progression; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
D005819:Genetic Markers