Diagnostic performance of the urinary bladder carcinoma antigen ELISA test and multiparametric DNA/cytokeratin flow cytometry in urine voided samples from patients with bladder carcinoma.

ABSTRACT

BACKGROUND: The objective of the current study was to comparatively analyze the sensitivity and specificity of flow cytometric DNA/cytokeratin 8/18 measurements and the urinary bladder carcinoma antigen (UBC) enzyme linked immunoabsorbent assay (ELISA) test for the detection of bladder carcinoma in voided urine samples. METHODS: Eighty-one fresh urine voided samples, preserved frozen for a maximum period of 3 months, belonging to patients with an active bladder carcinoma (n = 37), patients who were free of disease as confirmed by cystoscopy (n = 19), patients receiving intravesical therapy (n = 17), and individuals with other benign and malignant conditions (n = 8), were collected. Flow cytometry measurements of thawed samples were based on the detection of cytokeratin (CK) 8+ and CK18+ cells using the 3F3 and 6D7 monoclonal antibodies alone or in combination with the measurement of cell DNA contents, after propidium iodide staining. Urinary bladder carcinoma antigen test was measured by ELISA. RESULTS: Patients were grouped according to the presence (n = 44) or absence (n = 29) of bladder carcinoma as confirmed by cystoscopy, and taking cutoffs of 9.7 microg/L for UBC-ELISA, 75% for the percentage of 3F3 (+) and 6D7 (+) cells, and 10.6% for the proportion of hyperdiplod cells that suggested a specificity of 83%, the individual sensitivity obtained for each parameter was 77%, 5%, 9%, and 77%, respectively. The presence of DNA aneuploid populations showed a relatively low sensitivity (36%) although it was the most specific parameter (93%). Combining UBC antigen test with the proportion of cells showing DNA content higher than 2n increased to 89% the sensitivity of the UBC antigen alone. However, false-positive results for both techniques were found in individuals with urologic diseases other than bladder carcinoma and in patients receiving intravesical therapy. CONCLUSIONS: The authors' results suggest that the combined use of the UBC antigen test and DNA/cytokeratin flow cytometry double stainings for the analysis of freshly obtained urine voided samples, cryopreserved to assure cellular integrity, is of great clinical utility for the detection of tumor recurrence in patients with bladder carcinoma.