Nuclear matrix protein‐22: a prospective evaluation in a population at risk for bladder cancer. Results from the UroScreen study

Abstract

What ' s known on the subject? and What does the study add?The prognosis of bladder cancer signifi cantly depends on tumour stage and time of diagnosis so early diagnosis is desirable to decrease mortality and treatment costs. The NMP22 test is approved for clinical application by the Food and Drug Administration (FDA) of the US. Previous studies have reported values of 47 -100% for sensitivity and 58 -91% for specifi city with this test, but there is no new data on the predictive value of NMP22 for screening bladder cancer (BC). The most important risk factor for BC is the tobacco consumption but occupational exposure to carcinogenic substances, especially aromatic amines, is regarded as another risk factor.The UroScreen study is a prospective longitudinal study for the early detection of BC. To our knowledge, it is the largest prospective validation study conducted over the longest period of time. The study results led us to conclude that, based on the currently available data, NMP22 should not be regarded as an alternative to endoscopy, and we could not make a general recommendation for screening or follow-up. The UroScreen results indicate that urine-based molecular markers could be a suitable addition to urine cytology and the detection of microhaematuria. OBJECTIVE• To evaluate the value of nuclear matrix protein-22 (NMP22) in bladder cancer (BC) screening, and its effect on variables in a prospective study in a high-risk population. PATIENTS AND METHODS• A total of 1772 chemical workers (mean age 62 years) exposed to carcinogenic aromatic amines were enrolled in the study.• In all, 7091 screening check-ups in 1609 subjects were performed.• Urine samples were collected for a quantitative NMP22 immunoassay, urine analysis and creatinine concentration assessment.• Cystoscopy and subsequent transurethral resection were performed where there were suspicious fi ndings. RESULTS• Histopathological analysis found three papillary urothelial neoplasms of low malignant potential, fi ve recurrent BCs and 13 primary BCs. Three tumours were at a muscle-invasive stage (pT2, pT3a or pT3b).• We found higher NMP22 concentrations ( > 10 U/mL) in 224 patients, which correctly predicted BC in six cases (sensitivity 97.29%, specifi city 28.57%; negative predictive value 99.04%, positive predictive value 12.24%).• Gross haematuria affected NMP22 results (odd ratio [ OR ] 3.49, 95% confi dence interval [ CI ] 1.81 -6.73). Infection also affected NMP22 results (OR 4.13,).• NMP22 was more frequently positive in urine with creatinine concentration > 2.5 g/L (OR 1.61, 95% CI 0.91 -2.86). CONCLUSIONS• NMP22 outcomes are affected by haematuria, infection and concentrated urine.• NMP22 alone cannot be recommended for primary screening in a high-risk population nor as an alternative to cystoscopy during follow-up.• A NMP22 test might be a useful adjunct to urine cytology. KEYWORDSbladder cancer , early detection , renal function , NMP22 , haematuria Study Type -Diagnostic (non-consecutive cohort without consistently applied reference st...

Developing proteomic biomarkers for bladder cancer: towards clinical application

“…Unfortunately this performance has not always been reproduced when the assays are evaluated in independent patient populations (Table 1). 25,26 This finding is most evident from the results of the UroScreen study, wherein NMP22® was used to screen a population with a high risk of bladder cancer owing to previous chemical exposures; the specificity of NMP22® was found to be only 29%. 25 A similar observation was evident for the UroVysion® assay, in which the reported sensitivity was only 45%.…”

“…25,26 This finding is most evident from the results of the UroScreen study, wherein NMP22® was used to screen a population with a high risk of bladder cancer owing to previous chemical exposures; the specificity of NMP22® was found to be only 29%. 25 A similar observation was evident for the UroVysion® assay, in which the reported sensitivity was only 45%. 26 ImmunoCyt™ also proved to be less effective when tested in 506 patients with atypical urinary cytology, resulting in a specificity of 49%.…”

The value of the NMP22 test for superficial bladder cancer diagnosis and follow-up

“…In a recent study which enrolled 1609 risky factory employees who were working with a chemical substance containing aromatic amine, diagnostic sensitivity, specificity, negative, and positive predictive values of NMP22 test were 97.2, 28.5, 99, and 12.2%, respectively. [9] In a study performed by Tritschler et al [5] on 100 patients without previous diagnosis of bladder cancer, sensitivity, and specificity of the NMP22 test, and cytology were found to be 65 vs 44%, and 40 vs. 78%, respectively. The authors concluded that with lower sensitivity, and specificity rates NMP22 could not be recommended in daily practice as a bedside test in the diagnosis, and monitorization of the bladder cancer.…”

Imidazolium Salts as Small-Molecule Urinary Bladder Exfoliants in a Murine Model

“…In addition, postresection monitoring in bladder cancer patients may involve both cytology and other biomarker-based methods (e.g., detection of nuclear matrix protein 22). However, the utility of these newer approaches is not universally accepted, especially across distinct patient populations and clinical situations (35), and additional biomarkers and methodologies are under study. Topical administration of an exfoliant would provide a much richer sample for cytologic analysis, likely increasing the sensitivity of cell-based diagnostics.…”