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.

نویسندگان

  • Thorsten H Ecke
  • Horst H Schlechte
  • Guntram Schulze
  • Severin V Lenk
  • Stefan A Loening
چکیده

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 immunoluminometric assay LIA-mat TPA-MProlifigen. 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 68.37%, 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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Metabolism of tumour-derived urokinase receptor and receptor fragments in cancer patients and xenografted mice.

The urokinase-type plasminogen activator receptor (uPAR) is involved in cell migration and tissue remodelling, as a receptor for pro-uPA, as a cell adhesion component, and in a soluble form as a chemoattractant.We have analyzed the presence and the molecular forms of uPAR and uPAR-fragments in urine of ovarian cancer patients in comparison with tumour tissue, ascites, and serum. Carcinoma tissu...

متن کامل

Assessment of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in Breast Cancer Tissue: Historical Aspects and Future Prospects.

centration of tPA in plasma amounts to 5–10 ng/ml, but varies strongly under different physiological and pathological conditions. Although it was already known before 1970 that plasminogen activator activity may be increased in tumour tissues over non-neoplastic tissue, for some time, interest was turned away from the possible role of plasminogen activators in cancer progression [15–20], partic...

متن کامل

Regulation of Plasminogen Activation

The main components of plasminogen activation include plasminogen, tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR), and plasminogen activator inhibitors-1 and -2 (PAI-1, PAI-2 ). uPA and its receptor uPAR are known to be important in cell migration/adhesion. In these studies, we show that uPAR was anchored in focal conta...

متن کامل

uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder – Possible Clinical Implications

The objective of the present study was to confirm the expression and localisation pattern of the urokinase-type plasminogen activator receptor (uPAR) focusing on its possible clinical relevance in patients with urothelial neoplasia of the bladder. uPAR is a central molecule in tissue remodelling during cancer invasion and metastasis and is an established prognostic marker in various cancer dise...

متن کامل

Antigen levels of urokinase-type plasminogen activator receptor and its gene polymorphism related to microvessel density in colorectal cancer.

We determined the distribution of genotypes and frequencies of alleles of the (CA)(n) repeat polymorphism in intron 3 of the urokinase plasminogen activator receptor (uPAR) gene, uPAR antigen levels and microvessel density (MVD) in tumour and distant mucosa samples from 52 patients with colorectal cancer. The uPAR level was higher for patients with high MVD comparing to patients with lower MVD ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Anticancer research

دوره 25 1B  شماره 

صفحات  -

تاریخ انتشار 2005