TY - JOUR
T1 - Influencing factors on the NMP-22 urine assay
T2 - An experimental model
AU - Miyake, Makito
AU - Goodison, Steve
AU - Giacoia, Evan Gomes
AU - Rizwani, Wasia
AU - Ross, Shanti
AU - Rosser, Charles J.
N1 - Funding Information:
This work was supported by research grants from the Florida Department of Health James and Esther King Team Science Award 10KT-01 (CJR), the National Cancer Institute RO1 CA116161 (SG), and the Flight Attendant Medical Research Institute (CJR).
PY - 2012
Y1 - 2012
N2 - Background: 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. 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. Methods. Pooled 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. Results: Urines from control subjects were negative for NMP-22. The addition of whole blood at 50ul/10ml, 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 (306g protein) resulted in a false-positive result. High concentrations of pooled-cancer cells (106) or cell lysate (30.6g 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%. Conclusions: Rather 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.
AB - Background: 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. 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. Methods. Pooled 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. Results: Urines from control subjects were negative for NMP-22. The addition of whole blood at 50ul/10ml, 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 (306g protein) resulted in a false-positive result. High concentrations of pooled-cancer cells (106) or cell lysate (30.6g 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%. Conclusions: Rather 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.
KW - Bladder cancer
KW - NMP-22
KW - Urine
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U2 - 10.1186/1471-2490-12-23
DO - 10.1186/1471-2490-12-23
M3 - Article
C2 - 22928931
AN - SCOPUS:84865317555
SN - 1471-2490
VL - 12
JO - BMC Urology
JF - BMC Urology
M1 - 23
ER -