The use of urinary nuclear matrix protein 22 (NMP22) as a diagnostic adjunct to urine cytology for monitoring of recurrent bladder cancer--institutional experience and review

Diagn Cytopathol. 2015 Apr;43(4):307-14. doi: 10.1002/dc.23239. Epub 2014 Dec 8.


Background: This prospective study compares urine NMP22 immunoassay and cytomorphology for detecting recurrent urothelial carcinoma (UC) of the bladder and correlates between NMP22 levels and grade, multiplicity, and size of the tumor. We aimed refining the use of NMP22 test in the management of UC at our institution.

Methods: Urine specimens, collected prior to a cystoscopic biopsy either from patients with a history of bladder cancer (n = 50) or from controls (n = 15) were studied. Cytology and NMP22 results were compared with subsequent biopsies and performance characteristics were measured.

Results: Overall sensitivity and specificity of cytology was 62.5% and 87.5%, respectively while NMP22 had a sensitivity of 85.4% and specificity of 76.5%. NMP22 was superior to cytology for detecting low-grade UC (82.6% vs. 54.5%) and in terms of NPV (65% vs. 44.4%) while cytology reached 100% detection rate for high-grade UC. And, the sensitivity of 98% was achieved when NMP22 was combined with atypical cytology. Optimal performance of NMP22 has been detected around the reference value of 6.4 U/ml. The mean NMP22 values in control and study groups were 2.5 U/ml and 36 U/ml, respectively. The mean NMP22 value was 20.9 U/ml in low-grade UC and 53.2 U/ml in high-grade category.

Conclusions: The NMP22 values displayed higher sensitivity for low-grade UC while cytology was highly sensitive and spesific in detection of high-grade UC. Combining urine NMP22 assay with atypical cytology improved sensitivity for detection of recurrent UC. The inclusion of the adjunctive NMP22 test in monitoring protocols for low-grade UC in combination with cytology for high-grade UC could enable clinicians to decrease the frequency of follow-up cystoscopies.

Keywords: NMP22; performance; recurrence; urine cytology; urothelial carcinoma bladder.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / urine*
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / urine*
  • Cystoscopy / methods
  • Female
  • Humans
  • Immunoassay / methods
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / urine*
  • Neoplasm Staging
  • Nuclear Proteins / urine*
  • Prospective Studies
  • Sensitivity and Specificity
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / urine*
  • Urine / cytology


  • Biomarkers, Tumor
  • Nuclear Proteins
  • nuclear matrix protein 22