Immunostaining of cytokeratin 20 in cells from voided urine for detection of bladder cancer

Purpose: Cytokeratin 20 is a cytoskeletal protein expressed in colon and bladder cancer cells but only rarely in normal urothelium. Previous studies have shown that identification of RNA coded for cytokeratin 20 in urine samples using polymerase chain reaction is highly sensitive for detection of bladder tumors. We examined the efficacy of immunocytology on cells from voided urine samples using monoclonal antibodies against cytokeratin 20 for noninvasive detection of bladder tumors. Materials and Methods: A total of 174 patients comprised the study, including 80 who were evaluated because of hematuria or irritative voiding symptoms and 94 who were examined during followup visits after resection of bladder tumors. Voided urine samples were obtained for immunocytology and cytopathology. Each patient underwent cystoscopy, and biopsies were done when a bladder tumor was detected or carcinoma in situ was suspected. Indirect immunoperoxidase staining was done on cytocentrifuge slides using a monoclonal antibody against cytokeratin 20, Results: Bladder tumors were found in 87 patients. Immunocytology resulted in 81.6% sensitivity, 77% specificity and 80% accuracy. False-negative results occurred in 12 patients with superficial low grade tumors and in 4 with high grade invasive tumors. Cytopathology resulted in 51.7% sensitivity and 94.2% specificity. Conclusions: Immunocytology of the cytokeratin 20 antigen is significantly more sensitive than cytopathology for bladder tumor detection, especially low grade and low stage cancer. The results are not affected by inflammation or previous treatments with bacillus Calmette-Guerin. Immunocytology may miss high grade tumors and, therefore, cannot be used alone as a substitute for cystoscopy.