Four Tumour Markers for Urinary Bladder Cancer - Tissue Polypeptide Antigen (TPA), HER-2/neu (ERB B2), Urokinase-type Plasminogen Activator Receptor (uPAR) and TP53 Mutation

Purpose: Tissue polypeptide antigen (TPA) is present in the proteolytic fragments of cytokeratins 8, 18 and 19 as a component of the cytoskeleton of nonsquamous epithelia. HER- 2/neu protein is a transmembrane tyrosine kinase cell surface growth factor receptor that is expressed on normal epithelial and some cancer cells. The urokinase-type plasminogen activator receptor (uPAR) is a GPI-linked single-chain glycoprotein. Mutations of the tumour suppressor gene P53 (TP53) are frequently correlated with tumour development and progression. We compared TPA, HER-2/neu and uPAR, and TP53 mutation in tumour-free and bladder cancer patients. Materials and Methods: Clinical samples were used from 60 patients with tumours of the urinary bladder and from 9 patients with benign urological diseases. TPA was analyzed by the immuno- luminometric assay LIA-mat® TPA-M Prolifigen®. HER-2/neu was measured using the Bayer Oncoprotein test. uPAR was measured with the IMUBIND® Total uPAR ELISA Kit. Mutation status in TP53 exons 5, 6, 7 and 8 was analyzed by temperature gradient gel electrophoresis of exon-specific PCR products and by sequence analysis. Statistical analysis included ROC, Mann-Whitney U-test and Pearson's correlation. Results: Pathological concentrations of TPA, HER-2/neu and uPAR are detectable in the serum and in urine of bladder cancer patients. The calculated diagnostic sensitivity for TPA in serum was 68.3%, for TPA in urine 33.3%, for HER-2/neu 86.7% and for uPAR 79.5%. Pathological levels of TPA in serum (p=0.001) and HER-2/neu (p=0.001) were significantly higher in patients with bladder cancer in comparison to the control group. For superficial bladder cancer, the mutation frequency in TP53 was 50%, while for invasive bladder cancer the mutation frequency in TP53 was 100%. Elevated TPA, HER-2/neu and uPAR levels were associated with all grades and stages of bladder cancer. Conclusion: TPA, HER-2/neu or uPAR can differ between bladder cancer patients and the control group, but not between superficial and invasive bladder cancer. TP53 mutation frequently occurs in higher stages of bladder tumours.