CYTOKERATIN-20 - A NEW MARKER FOR EARLY DETECTION OF BLADDER CELL-CARCINOMA

Purpose: Cytokeratins are constituents of the intermediate filaments o f epithelial cells in which they are expressed in various combinations depending on epithelial type and degree of differentiation. Of the 20 known cytokeratins, cytokeratin 19 is expressed in normal urothelium cells, whereas the recently identified cytokeratin 20 (CK-20) is expre ssed in urothelial carcinoma but not normal urothelium cells. We exami ne whether CK-20 expression can be used as a bladder tumor marker for transitional cell carcinoma in cells isolated from urine. Materials an d Methods: The reverse transcriptase polymerase chain reaction method was used to determine expression of CK-20 in cells separated from urin e of patients with bladder carcinoma. Cells were obtained from urine o f 192 patients stratified into 3 groups of 21 healthy young volunteers without a history of transitional cell carcinoma, 27 with a negative bladder biopsy for transitional cell carcinoma and 144 with bladder tr ansitional cell carcinoma. The parameters were tumor stage and grade, tumor size, number of tumors, urinary cytology and CK-20. Results: CK- 20 amplification band (370 base pairs) was obtained with messenger rib onucleic acid extracted from transitional cell carcinoma cells of blad der tumor. CK-20 in the urine samples of the control group was negativ e (no false-positive results, specificity 100%). Among the 27 patients with pTo disease CK-20 was negative in 20 (specificity 74.1%). In the 7 patients with positive CK-20 histology showed chronic inflammation in 2, atypical hyperplasia in 3 and metaplasia in 1. In 1 patient who had a known history of transitional cell carcinoma the urothelium was normal. Among 144 patients with bladder transitional cell carcinoma CK -20 was positive in 131. Sensitivity of the method was much higher tha n urinary cytology (91 versus 56.3%, p <0.0001). We demonstrated no co rrelation between CK-20 and tumor grade. Conclusions: Our results indi cate that CK-20 is a potential marker for bladder cancer. The noninvas ive detection method assesses urothelial cells from the voided urine s pecimen using reverse transcriptase-polymerase chain reaction. The CK- 20 marker was significantly more sensitive than urinary cytology.