Influence of hematuria and infection on diagnostic accuracy of urinary LASP1: a new biomarker for bladder carcinoma.

AIM: To further promote the clinical use of urinary LASP1 as biomarker for urothelial carcinoma of the bladder regarding limitations and alternative testing systems. PATIENTS & METHODS: Urine stabilization, alternative measurement systems and limitations by erythrocyte contamination and infection were investigated in 246 patients. RESULTS: Thimerosal allowed sufficient stabilization. Fluorescence-activated cell sorting analysis was not influenced by presence of erythrocytes or leukocytes and reliably urothelial carcinoma of the bladder but cell counts in specimen were low. Cut-off values of <25 leukocytes and <200 erythrocytes/µl resulted in sensitivity, specificity, positive and negative predictive values of 0.59, 0.80, 0.80 and 0.59, respectively. CONCLUSION: Hematuria up to 200 erythrocytes/µl but not presence of leukocytes may be tolerated for this promising marker.

LASP-1, a novel urinary marker for detection of bladder cancer.

OBJECTIVES: The LIM and SH3 (LASP)-1 protein is a focal adhesion protein that has been linked to oncogenesis. The aim of this study was to evaluate the diagnostic use of the detection of LASP-1 in tumor specimens and in urine for noninvasive detection of transitional cell carcinoma (TCC). MATERIALS AND METHODS: Immunohistochemical staining for LASP-1 was performed on 72 archived bladder tumor specimens, and LASP-1 content was measured in 132 spontaneous urine sample sediments by Western blot analysis. RESULTS: In the histologic specimens, immunohistochemical staining for LASP-1 showed abundant expression throughout the urothelium of the bladder and ureter. However, modest overexpression of LASP-1 was observed in the TCC specimens. Measurement of the LASP-1 protein concentrations in urinary cell pellets from healthy donors and bladder cancer patients was highly sensitive for the presence of TCC. The cut-off value was determined by receiver operating characteristic (ROC) analysis. When a cut-off value of 1 ng LASP-1/500 µl of urine was used, the sensitivity, specificity, and positive and negative predictive values of the assay were 83.1%, 85.3%, 83.1%, and 80.6%, respectively.The increased urinary LASP-1 content in TCC patients was attributable in part to a specific increase in cell shedding presumably caused by changes in cell adhesion, as confirmed by LASP-1 knockdown. Contamination with erythrocytes above 250 cells/µl and urinary infection gave false positive results and are therefore sample exclusion criteria. CONCLUSIONS: In the absence of urinary infection or gross hematuria, urinary LASP-1 level is a promising marker for transitional cell carcinoma.