Urinary survivin mRNA expression and urinary nuclear matrix protein 22 BladderChek[R] and urine cytology in the detection of transitional cell carcinoma of the bladder

To compare the diagnostic performance of urine cytology [UC], survivin mRNA expression, and the NMP22 BladderChek[R] [NMP22BC] test for the detection, grading and staging of transitional cell carcinoma [TCC] of the bladder. Voided urine samples collected from 25 healthy controls and 80 patients diagnosed with TCC of the bladder were subjected to UC, the NMP22BC test and reverse-transcription real-time PCR for survivin mRNA expression. Survivin mRNA expression showed the highest sensitivity [87.5%] followed by the NMP22BC test [61.3%] while UC exhibited the lowest sensitivity [40%]. All three urine markers had a similar specificity of 96% [95% CI 80.5-99.3%]. Survivin mRNA expression was the only urine marker that showed a significant difference in relation to tumour histological grade [X[2] 8.5, p = 0.015]. None of the three urine markers was significantly related to tumour pathological stages. The diagnostic sensitivity of urinary urviving mRNA expression was superior to that of UC and the NMP22BC test and correlates with tumour pathological grade but not stage

Patients with a negative cystoscopy and negative Nmp22® Bladderchek® test are at low risk of missed transitional cell carcinoma of the bladder: a prospective evaluation

OBJECTIVES: Urine based tumor markers have uncertain utility in diagnosis or surveillance of patients with bladder cancer while cytology is commonly used. We evaluated whether cytology provides additional diagnostic information in patients with a negative NMP22® BladderChek® test (BladderChek) and negative cystoscopy. MATERIALS AND METHODS: We performed subset analyses of 2 large prospective multi-center databases evaluating BladderChek for UCB detection and surveillance. These cohorts were analyzed for presence of cancer and result of urine cytology in setting of a negative cystoscopy and negative BladderChek. Subsequently, we prospectively performed cystoscopy, cytology and BladderChek on 434 patients at our institution being evaluated for UCB. RESULTS: In the detection database (n = 1331), 1065 patients had a negative cystoscopy and BladderChek. There were 3 cancers (stages Ta, Tis and T1) and cytology was atypical in one and reactive in two. In the surveillance cohort (n = 668) patients, 437 patients had negative cystoscopy and BladderChek. Cancer was found in 2 patients (stages Tis and Ta). The patient with Tis has dysplastic cytology and Ta tumor had reactive cytology. In our cohort of 434 patients, 288 pts had negative cystoscopy and BladderChek. One cancer was missed, a Ta ureteral urothelial carcinoma with a reactive cytology. CONCLUSIONS: In patients with negative cystoscopy and BladderChek, very few cancers are missed and cytology was not effective in detection. Use of a point-of-care test in conjunction with cystoscopy in lieu of cytology could decrease cost, provide immediate results, improve negative predictive value and reduce the uncertainty that results from inconclusive cytologic results.

Urine concentration of nuclear matrix protein 22 for diagnosis of transitional cell carcinoma of bladder

The aim of this study was to determine the diagnostic value of urine nuclear matrix protein 22 [NMP22] level in detection of transitional cell carcinoma [TCC] of the bladder. A total of 76 patients with newly-diagnosed or recurrent TCC and 75 controls without urinary tract disorders participated in this study. A urine sample was obtained for measurement of the NMP22 level using the enzyme-linked immunoabsorbent assay. The resulted values were evaluated in comparison with the results of pathologic examination. A total of 76 patients with TCC of the bladder and 75 volunteers without TCC were enrolled in the study. The mean level of urine NMP22 had an increasing trend associated with tumor grade [P = .01] and tumor stage [P < .001]. In participant without TCC, the mean urinary NMP22 level was 5.48 +/- 6.34 U/mL, while this value was 25.01 +/- 35.33 U/mL in patients with TCC of the bladder [P < .001]. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of urine NMP22 for detection of TCC were 75.5%, 86.7%, 85.1%, 77.4%, and 80.8%, respectively. The sensitivity of NMP22 in detecting stage Ta tumors appeared to be low [31.3%], but for grade 1 tumors, the sensitivity was 66.7%. Measurement of urine NMP22 is a noninvasive, highly sensitive, and specific method for detecting TCC of the bladder and estimating its grade and stage. Further studies can be helpful to determine whether it can be used in clinical practice

Evaluation of Urine NMP22 Point-of-Care Test for the Screening of Bladder Cancer / 대한진단검사의학회지

BACKGROUND: Screening of high-risk patients using bladder tumor markers can offer an advantage of early detection and saving medical costs. For these purpose many tumor markers have been developed to supplement invasive cystoscopy. Our study evaluated the NMP22 point-of-care test (NMP22 POCT), which is one of the tumor makers, comparing with the standard urine cytology for the diagnosis of bladder cancer. METHODS: From January to September 2005, 232 patients who had undergone a cystoscopy due to bladder cancer associated symptoms including hematuria and dysuria were enrolled in this study. Urine specimens were collected for NMP22 POCT and cytology. NMP22 POCT and urine cytology were compared for sensitivity and specificity. In addition, we evaluated urine stick test and microscopy to explain some false-positive results in NMP22 POCT. RESULTS: Superficial transitional cell carcinoma was diagnosed in 10 patients. The sensitivity of NMP22 test was 60% (95% confidence interval [CI], 26.2-87.8%), whereas that of cytology was 33.3% (95% CI, 7.5-70.1%); however, the difference was not significant. The specificity of NMP22 test was 69.8% (95% CI, 63.3-75.8%), compared with 99.0% (95% CI, 96.5-99.9%) for cytology (P<0.001). The presence of microscopic RBCs in urine specimen was significantly associated with the lower specificity of NMP22 POCT (P=0.02). CONCLUSIONS: NMP22 POCT was significantly less specific than urine cytology. To be useful as a bladder cancer screening test, the NMP22 test should have a higher specificity.

Usefulness of NMP22 BladderChek for the Diagnosis and Monitoring of Bladder Cancer / 대한진단검사의학회지

BACKGROUND: As bladder cancer is a superficial tumor with frequent recurrences, early detection and confirmation of recurrence are important. We evaluated the usefulness of NMP22 BladderChek (NMP22BC) for the diagnosis and monitoring of bladder cancer. METHODS: From July to December 2004, we enrolled in the study 670 patients who visited the urology clinic in Ewha Womans University, Dongdaemun Hospital with hematuria or dysuria and were tested with NMP22BC. We also performed the NMP22BC and BTA stat tests simultaneously in 21 patients and interference test in 10 patients. RESULTS: NMP22BC tests were negative in 97% of the patients who had been cured of bladder cancer and were positive in 95% of the patients with recurred bladder cancer. The diagnostic sensitivity, specificity, positive and negative predictive value, and efficiency were 95.0%, 91.5%, 25.7%, 99.8%, and 91.6%, respectively, with 8.5% false positive and 5% false negative rates. Fifty-five patients showed false positive in the NMP22BC test, the main cause of which was the presence of WBCs in urine. There was a good agreement between the NMP22BC and BTA stat tests (kappa agreement value, 0.5; P=0.008). According to the interference test, two patients with more than 3+ in leukocyte esterase results showed false positive in the NMP22BC test. CONCLUSIONS: NMP22BC test was simple to perform, rapid to produce the results, and useful in diagnosing a bladder cancer recurrence; the test shows a high efficiency with a high sensitivity, specificity, negative predictive value, and low false negative rate.

Evaluation of the NMP22 test and comparison with voided urine cytology in the detection of bladder cancer

The purpose of this study was to assess the clinical performance of the NMP22 test and to compare it with that of voided urine cytology for the detection of bladder cancer. The NMP22 test was evaluated in two groups of patients. The first group was comprised of patients with histologically confirmed active transitional cell carcinoma (TCC) of the bladder, and the second group contained those with a history of bladder TCC but that were considered to have no evidence of disease on the basis of cystoscopic evaluation of bladder and/or biopsy. Sensitivity was determined in voided urine samples from patients with active TCC of the bladder. Specificity was determined in the urine samples of patients with a history of bladder TCC but no current evidence of disease. The NMP22 test was positive in 53 of 70 samples from patients with active bladder TCC. The sensitivity of the NMP22 test (75.7%) is significantly better than that of voided urine cytology (55.7%). The specificity of the NMP22 test and of voided urine cytology were 72.2% and 88.9% respectively, in patients with a history of bladder TCC but no current evidence of disease. There was no significant difference between the specificity of NMP22 and that of urine cytology. The NMP22 test is superior to voided urine cytology in the detection of TCC of the bladder. The results of this study indicate that the NMP22 test is an useful adjunct to cystoscopy in the detection and monitoring of TCC of the bladder.