1286 STEPWISE APPLICATION OF IMMUNOCYTOLOGY AND FISH IN THE SURVEILLANCE OF PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER

Abstract

detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. METHODS: We performed a case-controlled validation study in which voided urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (Interleukin-8 (IL-8), Matrix metalloproteinase-9 (MMP-9), Matrix metalloproteinase-10 (MMP-10), Syndecan 1 (SDC1), Chemokine (C-C motif) ligand 18 (CCL18), plasminogen activator inhibitor-1 (PAI-1), CD44, vascular endothelial growth factor (VEGF), Angiogenin (ANG), Carbonic anhydrase 9 (CA9), Alpha 1-Antitrypsin (A1AT), Osteopontin (OPN), Pentraxin3 (PTX3), and Apolipoprotein E (APOE)) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. RESULTS: An 8-biomarker diagnostic signature achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%). Subsequently, the validate diagnostic signature was tested by ELISA in an independent cohort of 308 patients (102 tumor bearing subjects and 206 diverse controls including UTI, stones, voiding symptoms, hematuria and normals). The 8-biomarker diagnostic signature was accurate in diagnosing BCa in voided urine samples (sensitivity 88%, specificity 91%). CONCLUSIONS: These data show that a multivariate urinebased assay can markedly improve the accuracy of non-invasive BCa detection. Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.