Objectives: We evaluated the diagnostic efficacy of urinary CD44 and cytokeratin 20 (CK20) mRNA in comparison with voided urine cytology (VUC) for the detection of bladder cancer.
Design and methods: A total of 136 Egyptian patients provided a single voided urine sample for CD44, CK20 mRNA and VUC before cystoscopy. Of the 136 cases, 111 were histologically diagnosed as bladder cancer whereas the remaining 25 had benign urological disorders. A group of 20 healthy volunteers was also included in this study. Voided urine was centrifuged and the urine sediment was used for cytology, estimation of CD44 by ELISA and RNA extraction. CK20 mRNA was detected by conventional RT-PCR and quantitative real-time RT-PCR.
Results: The best cutoff values for CD44 and relative CK20 mRNA detected by real-time RT-PCR were calculated by receiver operating characteristic curve. The positivity rates and the mean ranks for CD44 and CK20 mRNA showed significant difference among the three investigated groups (p=0.001). Quantitative real-time RT-PCR results were comparable to conventional RT-PCR for the detection of CK20 mRNA. The positivity rate of CD44 was significantly associated with schistosomiasis and urine cytology. The overall sensitivity and specificity were 52.3% and 88.9% for VUC, 63.1% and 88.9% for CD44, and 82.0% and 97.8% for CK20 mRNA. Combined sensitivity of VUC with CD44 and CK20 mRNA together (95.5%) was higher than either the combined sensitivity of VUC with CD44 (78.4%) or with CK20 mRNA (91.0%) or than that of the biomarker alone.
Conclusion: Urinary CD44 and CK20 mRNA had higher sensitivities compared to VUC. However, when the diagnostic efficacy was considered, CK20 mRNA by either conventional RT-PCR or real-time RT-PCR had the highest sensitivity and specificity compared to CD44 and VUC.