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 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.

How to express tumor markers in bronchoalveolar lavage.

INTRODUCTION: Bronchoalveolar lavage (BAL) is a fundamental technique in the diagnosis of different respiratory diseases including lung cancer. Tumor marker values can be determined in the BAL fluid, but controversy still exists about how to express the results. OBJECTIVE: The aim of this study was to determine the best method of expressing tumor markers in BAL, either referring to total proteins or volume of fluid recovered. PATIENTS AND METHODS: A prospective, randomized, non-blind study was carried out. Seventy-six patients (72 men and 4 women) diagnosed with lung cancer and 17 subjects without respiratory disease were included. BAL was performed in all patients and the fluid retrieved was divided into two fractions: a bronchiolar fraction (F0) and an alveolar fraction (F1). Five tumor markers: cytokeratin fragment 19 (CYFRA 21-1), squamous cell carcinoma antigen (SCC), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and neuron-specific enolase (NSE) as well as total protein were measured in both fractions. The concentrations were expressed in relation to the volume of BAL fluid recovered (ng or mU/mL) and in milligrams of total protein of lavage fluid (ng or mU/mg TP). The SPSS 11.01 software was used for statistical analysis. Mann-Whitney U test and ROC curves were developed when significant differences were found. RESULTS: We found significant differences in the CYFRA 21-1 values in the two BAL fractions and in both ways of expressing its concentration; in SCC in F1 expressed in ng/mg TP; in TPA in F0 expressed in mU/mg TP; in TPS in both fractions expressed in mU/mg TP, and in NSE in both fractions in ng/mg TP. The markers that best differentiated tumors from controls (ROC curves) were CYFRA 21-1 in F0 and NSE in both fractions in ng/mg TP. CONCLUSIONS: Our study demonstrates that the concentrations of tumor markers in BAL expressed in relation to total protein were more effective than if expressed in mL of BAL fluid collected.

Effect of opium smoking on concentrations of carcinoembryonic antigen and tissue polypeptide antigen.

Previous studies have related opium and its pyrolysates to the risk of developing certain cancers. The aim of this work was to evaluate the clinical usefulness of determining carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) levels in habitual opium smokers. Serum CEA concentrations were measured in 128 opium smokers and in 44 controls of cigarette only smokers and 47 normal non-smokers by an EIA-based assay. TPA levels were also determined in serum and urine of a subgroup in the study population. The results indicated that serum CEA concentrations are higher in opium smokers than in healthy tobacco smokers (p = 0.004) and non-smokers (p = 0.001). The amount of opium used correlated with the serum CEA level (r = 0.276, p < 0.0001). The mean urine and serum TPA levels of the opium-addicted population were also higher than that of the non-smoking control group, but the differences were not statistically significant. We conclude that opium smoking is associated with elevated serum CEA levels. Therefore, for management of opium users with neoplastic diseases, increased levels of serum CEA should be viewed with caution to avoid misdiagnosis.