TP53 gene mutations as an independent marker for urinary bladder cancer progression.
This study evaluates the influence of the TP53 genetic status on tumour recurrence and progression with a highly effective electrophoretic technique. DNA from tissue of 75 non-invasive urinary bladder cancers was PCR amplified in the TP53 exons 5-8 and run on horizontal polyacrylamide gels under defined temperature conditions to yield specific gel shifts. Kaplan-Meier and Cox-Regression analysis were performed with tumour progression. The overall tumour recurrence in our patient population was 76.0% (57/75). Tumour recurrence frequency was 69.4% (34/49) in patients with TP53 wild-type, and 88.5% (23/26) in patients with TP53 mutation. There was no statistically significant difference with regard to recurrence frequency and time to recurrence. The progression-free survival was significantly shorter in patients with TP53 mutations, and the frequency of tumour progression was significantly higher in mutated as compared to wild-type tumours. Cox-Regression analysis showed a significant and independent influence of TP53 mutation on tumour progression in comparison with tumour grade, stage and history of prior bladder cancer. If segregated by exons, mutations in the DNA binding region of exon 8 seem to have a particular high influence on tumour progression. We conclude that genetic analysis of TP53 can select patients at high risk of bladder tumour progression that should be followed closely and may benefit from early radical surgical procedures.
Ecke
Thorsten H
TH
Department of Urology, HELIOS Hospital, Bad Saarow, Germany. tho_ecke@hotmail.com
Sachs
Markus D
MD
Lenk
Severin V
SV
Loening
Stefan A
SA
Schlechte
Horst H
HH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D016158:Genes, p53; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012008:Recurrence; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology
D014408:Biomarkers, Tumor