Tissue polypeptide antigen (TPA) in comparison with mutations of tumour suppressor gene P53 (TP53) in patients with bladder cancer.
BACKGROUND
Tissue polypeptide antigen (TPA) is a circulating complex of polypeptide fragments from cytokeratins 8, 18 and 19. It is a tumour-related protein. TPA is an indicator of higher cell proliferation. One function of TP53 is the suppression of apoptosis. TP53 mutations are frequently correlated with tumour development in bladder cancer. One function of TP53 is the suppression of apoptosis. We compared TPA expression and TP53 mutation analysis in tumour-free and bladder cancer patients.


METHODS
We examined 93 patients with bladder cancer, 24 patients with benign urological diseases and a control group of 18 healthy individuals. TPA concentration was measured by immunoluminometric assay with LIA-mat TPA-M Prolifigen. The normal cut-off value was defined at 47 U/I for serum and at 60 U/mmol for creatinine. Screening for TP53 mutations in tissue and urine sediment, amplification of the TP53 gene by polymerase chain reaction (PCR) for the exons 5, 6, 7 and 8 and temperature gradient gel electrophoresis (TGGE) were used to analyse the mutations. Statistical analysis included ROC, Mann-Whitney U-Test and Pearson's correlation.


RESULTS
For superficial bladder cancer the mutation frequency in TP53 was 44.8%. We found elevated TPA levels in 45.5% in serum and 36.1% in urine. For invasive bladder cancer the mutation frequency in TP53 was 79.2%. Elevated TPA levels were found in 57.7% in serum and in 58.3% in urine. TPA has a sensitivity of 48.9% in serum and 40.4% in urine; the specificity of TPA is 83% in serum and 100% in urine in comparison with healthy individuals. We found no correlation between TPA level and the inflammation status of the patient.


CONCLUSIONS
This study demonstrated that TP53 mutation frequently occurs in higher stages of bladder tumours. There was no TPA level difference between superficial and invasive bladder cancer. TPA is significantly higher in serum (p = 0.012) and in urine (p = 0.002) in patients with bladder cancer in comparison with control group. TPA in serum is significantly higher in patients with mutation of TP53 (p = 0.046) but not in urine (p = 0.173) in comparison with patients with wild-type TP53.
Ecke
Thorsten H
TH
Department of Urology, Humaine Hospital, Pieskower Str. 33, D-15526 Bad Saarow, Germany. tho eckeghotmail.com
Lenk
Severin V
SV
Schlechte
Horst H
HH
Loening
Stefan A
SA
D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine; D002455:Cell Division; D005091:Exons; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008163:Luminescent Measurements; D009154:Mutation; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D019396:Tissue Polypeptide Antigen / Q000097:blood* / Q000652:urine; D016159:Tumor Suppressor Protein p53 / Q000097:blood / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D014570:Urologic Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology
D014408:Biomarkers, Tumor; D019396:Tissue Polypeptide Antigen; D016159:Tumor Suppressor Protein p53