TP53 alterations as a potential diagnostic marker in superficial bladder carcinoma and in patients serum, plasma and urine samples.
Molecular markers are needed for better distinguishing of non-invasive papillary (pTa) and minimally invasive (pT1) bladder carcinomas and for identifying individual tumors with a high risk of recurrence or disease progression. First aim of our study was to evaluate TP53 microsatellite and mutation analysis as an effective concept for the characterization of superficial bladder tumors with different biological aggressiveness. Mutation screening in the TP53 hot spot region was performed in 55 microdissected superficial bladder tumor samples by direct genomic sequencing. PCR based LOH analysis was done with two markers at 17p13. Second, there is considerable interest in the development of non-invasive techniques that would detect recurrent bladder neoplasia. In order to evaluate TP53 alterations as a potential marker for a non-invasive diagnosis of recurrences or residuals and to determine whether tumor-specific DNA exhibiting LOH or sequences harbouring a mutation, can be detected in body fluids, mutation screening was performed in urine, plasma and serum of patients with a mutated primary tumor. LOH analysis with two markers at 17p was done in the corresponding urine and blood samples of 31 primary tumors. As seen from our results, TP53 inactivation by mutation seems to characterize higher malignant superficial bladder tumors which tend to recur and in which the probability is higher that the rezidives progress to muscle invasive growth pattern. Only in 2/8 cases, the TP53 mutation from the primary tumor could be re-detected in patients urine and blood. 17p microsatellite changes with at least one marker were found in 30/31 body fluids of the tumor patients (97%). Correlating the 17p status found in body fluids to the status of the primary tumor, the concordance is only about 52%. We conclude that TP53 genotyping as a non-invasive diagnostic tool in outpatient samples is of limited value for clinical practice.
Dahse
Regine
R
Klinikum der FSU Jena, Institut fur Humangenetik, D-07740 Jena, Germany. rdah@mti-n.uni-jena.de
Utting
Michael
M
Werner
Wolfram
W
Schimmel
Bettina
B
Claussen
Uwe
U
Junker
Kerstin
K
D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics*
D004273:DNA, Neoplasm