TP53 and p21WAF1/CIP1 behave differently in euploid versus aneuploid bladder tumours treated with radiotherapy.
The aim of this study was to examine any relation between DNA ploidy and previously detected TP53 (p53) or p21WAF1/CIP1 expression in 94 patients with muscle-invasive transitional cell carcinoma of the urinary bladder and to associate these factors with survival. DNA ploidy was determined by image cytometry. In a subgroup of patients, the mutational status of the TP53 gene was assessed by temporal temperature gradient electrophoresis (TTGE) or perpendicular denaturant gradient gel electrophoresis (DGGE) and subsequent sequencing. Significantly more aneuploid than euploid tumours showed TP53 accumulation (p = 0.003). Patients with aneuploid tumours lived longer than patients with euploid tumours (p = 0.003). In the euploid, but not in the aneuploid group, TP53 and p21WAF1/CIP1 were associated with cancer-specific survival (p = 0.002 and 0.02, respectively). Patients with > 50% TP53 expression had the longest survival time. Mutation analyses showed acceptable concordance with TP53 expression. We conclude that DNA aneuploidy may confer increased radiosensitivity in bladder cancer patients and that TP53 accumulation may confer increased radiosensitivity, but its effect is detectable only in euploid tumours.
Røtterud
R
R
Department of Pathology, The Norwegian Radium Hospital, Montebello, Oslo.
Skomedal
H
H
Berner
A
A
Danielsen
H E
HE
Skovlund
E
E
Fosså
S D
SD
D000782:Aneuploidy; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D004171:Diploidy; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D015993:Life Tables; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011836:Radiation Tolerance; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53