Abstract
BackgroundThe commercial NMP-22 urine assays for bladder cancer (BCa) detect nuclear mitotic apparatus protein 1 (NUMA1) using monoclonal antibodies. It remains unclear whether these assays are monitoring a tumor antigen or some other phenomenon associated with the disease state. In this study, we investigated the influence of urinary cellular and protein concentration, and hematuria on the performance of the NMP-22 tests in an experimental model.MethodsPooled urine from healthy subjects were spiked with varying concentrations of benign (UROtsa) cells, cancer cells (RT4, T24, KU-7 and UM-UC-14), whole blood or serum, prior to analysis with both NMP22® Bladder Cancer ELISA test and the NMP22® BladderChek® point-of-care test.ResultsUrines from control subjects were negative for NMP-22. The addition of whole blood at 50ul/10 ml, but not serum, resulted in a false-positive result. Furthermore, the addition of a high concentration of benign urothelial cells (106) or the cell lysate from these cells (306 μg protein) resulted in a false-positive result. High concentrations of pooled-cancer cells (106) or cell lysate (30.6 μg and above) resulted in a positive NMP-22 assay. Concordance between the NMP-22 ELISA assay and the NMP-22 point of care assay was >90%.ConclusionsRather than detecting a specific tumor antigen, urinary NMP-22 assays may be measuring the cellularity or amount of cell turnover that may be introduced into the urine by a variety of conditions, including surface shedding from bladder tumors. The absence of significant urinary cellularity in some cases due to lesion characteristics or the timing of sampling may result in false-negative NMP-2 assays.
Highlights
The commercial nuclear matrix protein-22 (NMP-22) urine assays for bladder cancer (BCa) detect nuclear mitotic apparatus protein 1 (NUMA1) using monoclonal antibodies
Noting the limitations of the bladder tumor antigen (BTA) assays, we investigated the influence of urinary cellular concentration, urinary protein concentration and hematuria on the performance of the NMP-22 tests in an experimental model
The NMP-22 level recorded for a pool of the four cancer cell lines was significantly higher than the NMP-22 level of UROtsa (24,299 ± 2,110 U/mg vs. 12,641 ± 1,973 U/mg, p < 0.05)
Summary
The commercial NMP-22 urine assays for bladder cancer (BCa) detect nuclear mitotic apparatus protein 1 (NUMA1) using monoclonal antibodies. It remains unclear whether these assays are monitoring a tumor antigen or some other phenomenon associated with the disease state. Non-invasive urine tests for the early detection or postsurgical surveillance of bladder cancer (BCa) are highly desirable for both patient and healthcare system. Voided urinary cytology (VUC) is the most widely used non-invasive urine test, with reported sensitivities ranging from 13–75% and specificities ranging from 85– 100% [1,2]. One is the bladder tumor antigen (BTA) test, which detects urinary complement factor H-related proteins using monoclonal antibodies [3]. Cortlandt Manor, NY, USA), are FDA approved for the detection
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