Urinary NMP22 Research Articles

Diagnostic accuracy of NMP-52, NMP-22 and urine cytology in the diagnosis of bladder cancer

Bladder cancer (BC) is the most important tumor problem of urologic cancer. Therefore, noninvasive urinary biomarkers were used for diagnosis of BC. However, the new biomarkers failed to reach higher accuracy. The aim of this study was to assess the diagnostic efficacy of nuclear matrix protein-22 (NMP- 22), nuclear matrix protein-52 (NMP-52), urinary cytology and to investigate combinations of urine NMP-52 with urinary cytology as noninvasive biomarkers to increase diagnostic performance of bladder cancer at different grades and stages. Overall, there were 156 subjects (62 BC, 54 cystitis patients and 40 healthy volunteers). The NMP-22 and NMP-52 were quantified in urine samples by ELISA. The urinary cytology is used by some physicians routinely for diagnosis of BC. The sensitivity and specificity for NMP-52 were 94% and 82%, for NMP-22 69% and 80.8% and for cytology 56% and 94.6% respectively and also, both urinary NMP-22 and NMP-52 have extremely significant relation (p<0.0001) to BC vs. healthy individuals and cystitis patients. Moreover, the combination of NMP- 52 with urinary cytology could predict all BC stages and grade with 95.6% sensitivity and 94.3% specificity. In conclusion, NMP-52 and urinary cytology in combination improve diagnostic performance for BC detection in different pathological types.

What are the currently available and in development molecular markers for bladder cancer? Will they prove to be useful in the future?

Urothelial carcinoma is the 9(th) most common cancer worldwide. Most urothelial tumors are non-muscle invasive on presentation. However, two-thirds of non-invasive bladder cancers will eventually recur with a 25% risk of progression to muscle-invasive bladder cancer. Tumor stage, histological grade and pathological invasion of blood vessels and lymphatic tissue are the main indicators for urothelial cancer prognosis. The gold standard for diagnosing bladder cancer is conventional white-light cystoscopy and biopsy. Urine cytology is a highly specific, sensitive test for high-grade tumors or carcinoma in situ (CIS). Urinary NMP22 has an overall sensitivity and specificity for detecting bladder cancer of 49% and 87%, respectively. However, there are false-positive results in the presence of urinary tract infection or hematuria. The detection of specific gene mutations related to urothelial cancers has been studied and employed to reproduce markers helpful for diagnosis. According to current studies, molecular markers can be used to predict tumor recurrence. From a prognostic point of view, new molecular markers have yet to be established as reliable indicators of tumor aggressiveness. We aimed to review the molecular markers with possible prognostic significance that have been discussed in the literature. This review examined the literature for various molecular markers under development for bladder cancer in an attempt to optimize patient care and reduce the costs of treating these patients.

Nuclear Matrix Protein 22 in Voided Urine Cytology Efficacy in Risk Stratification for Carcinoma of Bladder.

BackgroundTo investigate the nuclear matrix protein NMP22 in voided urine for detection of malignancy in patients with risk factors of symptoms of bladder cancer.MethodsJanuary 2009 to December 2012, participants included 1,331 patients at elevated risk for bladder cancer due to factors such as history of smoking or symptoms including hematuria and dysuria, patients at risk for malignancy of the urinary tract provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. The diagnosis of bladder cancer, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to cancer detection. Testing for the NMP22 tumor marker was conducted in a blinded manner.ResultsBladder cancer was diagnosed in 79 patients. The NMP22 assay was positive in 44 of 79 patients with cancer (sensitivity, 55.7%, 95% confidence interval (CI), 44.1-66.7%), whereas cytology test results were positive in 12 of 76 patients (sensitivity, 15.8%; 95% CI, 7.6-24.0%). The specificity of the NMP22 assay was 85.7% (95% CI, 83.8-87.6%) compared with 99.2% (95% CI, 98 initial endoscopy, including 3 that were muscle invasive and 1 carcinoma in situ.ConclusionThe noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the accuracy of cytoscopy, with test results available during the patient visit.

Urinary Tumor Markers Could Predict Survival in Bladder Carcinoma

The early diagnosis of bladder cancer is important for effective treatment of the disease. This study aimed to evaluate the nuclear matrix protein 22 (NMP 22), soluble epithelial cadherin (E-cadherin), cathepthin-D and total protein with clinico-pathological features of bladder cancer, and to determine the relation between each marker and tumor progression after treatment. The study includes 65 patients with bladder cancer, 14 benign urinary diseases and 11 healthy volunteers. Patients were categorized according to bilharzial infestation, T stage, tumor grade, size and the presence of lymph node metastasis. Forty patients were followed for disease progression after surgery. There was a significant increase of NMP22, E-cadherin, cathepthin-D and total protein detected in cancer group compared to healthy and benign groups. It was found that NMP 22 and E-cadherin had highest sensitivity (84.4, 76.9%, respectively) while, total ddedprotein showed highest specificity (77.4%). Tumor size correlated with urinary NMP22 (r=0.3, p=0.02), although, E-cadherin, cathepsin-D and total protein correlated with tumor size (r=0.3, 0.28, 0.2; p=0.01, p=0.01, 0.04, respectively) and lymph node metastasis (r=0.32, 0.34, 0.2; p=0.003, 0.005, 0.04, respectively). Elevated pretreatment urinary NMP22, E-cadherin and total protein levels was associated significantly with bladder cancer recurrence (p=0.02, 0.001, 0.005, respectively). In conclusion, determination of urinary NMP22, E-cadherin and total protein in bladder cancer patients or persons at risk of developing bladder cancer will help in early detection of the disease and prediction of recurrence. The use of a combination of tumor markers is markedly useful than the assessment of single one.

Influencing factors on the NMP-22 urine assay: an experimental model

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.

Influence of age on false positive rates of urine-based tumor markers

Several influencing factors on false positive rates (FPRs) of urine-based tumor markers in the detection of urothelial cancer (UC) have been identified. We evaluated age as a possible influencing factor. Urinary cytology (Cyt), UroVysion (FISH), ImmunoCyt (uCyt+) and NMP22 were determined in 1,554 patients suspicious for UC of the bladder before cystoscopy and in case of cancer detection before TURB. Additionally, upper urinary tract imaging was performed. Maker sensitivity, specificity and FPRs were evaluated in the entire cohort and in subgroups divided by age into <50, ≥ 50-70 and ≥ 70 years. Contingency tables and the Cochrane Armitage tests were used for statistical comparisons. UC was found in 377 and no UC in 1,177 (75 %) patients. A total of 336 patients were diagnosed with UC of the bladder and 41 with UC of the upper urinary tract. Overall sensitivity and specificity for Cyt were 82 and 82 %: for FISH, 73 and 79 % and for uCyt+, 79 and 75 %, respectively. For NMP22, regardless of the exclusion criteria they were 72 and 34 % and after exclusion of urinary tract infection (UTI) or prior to manipulation 46 and 86 %, respectively. Significantly higher FPRs were found with increasing age for Cyt (p = 0.001), a trend to higher FPRs for uCyt+ (p = 0.11) and almost no difference for FISH (p = 0.63). For NMP22, differences became significant after exclusion of patients with UTI or prior manipulation (p = 0.02). The results of the present study give evidence that false positive rates of Cyt and NMP22 increase with age indicating that age should be respected for their correct interpretation.

391 CLINICAL UTILITY OF NMP22 FOR BLADDER CANCER SURVEILLANCE A MULTI-CENTER CROSS-SECTIONAL STUDY

You have accessJournal of UrologyUrothelial Cancer: Natural History & Pathophysiology/Marker1 Apr 2012391 CLINICAL UTILITY OF NMP22 FOR BLADDER CANCER SURVEILLANCE A MULTI-CENTER CROSS-SECTIONAL STUDY Eugene K. Cha, Christopher E. Barbieri, Michael Rink, Thomas F. Chromecki, Allison Dunning, Yair Lotan, Harun Fajkovic, Douglas S. Scherr, Madhu Mazumdar, and Shahrokh F. Shariat Eugene K. ChaEugene K. Cha New York, NY More articles by this author , Christopher E. BarbieriChristopher E. Barbieri New York, NY More articles by this author , Michael RinkMichael Rink New York, NY More articles by this author , Thomas F. ChromeckiThomas F. Chromecki Graz, Austria More articles by this author , Allison DunningAllison Dunning New York, NY More articles by this author , Yair LotanYair Lotan Dallas, TX More articles by this author , Harun FajkovicHarun Fajkovic St. Poelten, Austria More articles by this author , Douglas S. ScherrDouglas S. Scherr New York, NY More articles by this author , Madhu MazumdarMadhu Mazumdar New York, NY More articles by this author , and Shahrokh F. ShariatShahrokh F. Shariat New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.455AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The urinary biomarker NMP22 has been FDA-approved for the surveillance of patients with bladder cancer. However, the use of NMP22 has not been widely incorporated into clinical practice. We sought to employ decision curve analysis to determine the impact of NMP22 on clinical decision-making for the surveillance of bladder cancer patients using data from a prospective trial. METHODS The study included 668 patients with a history of non-muscle-invasive bladder cancer who underwent cystoscopy, urine cytology, and measurement of urinary NMP22 levels. We constructed several prediction models to estimate risk of bladder cancer. The base model was generated using patient characteristics (age, gender, race, and history of intravesical therapy); cytology and NMP22 were added to the base model to determine effects on predictive accuracy. Clinical net benefit was calculated by summing the benefits and subtracting the harms and weighting these by the threshold probability at which a patient or clinician would opt for cystoscopy. RESULTS Ninety-seven patients were found to have recurrence of bladder cancer (14.5%). In univariable analyses, NMP22 was the strongest predictor of bladder cancer presence (predictive accuracy 66.0%), followed by cytology (56.5%) and history of intravesical therapy (56.4%). In multivariable prediction models, NMP22 improved the predictive accuracy of the base model by 11.5% (AUC 59.2% to 70.7%, p<0.0001) and that of the base model plus cytology by 6.4% (AUC 64.3% to 70.7%, p=0.036). Decision curve analysis revealed that adding NMP22 to other models increased clinical benefit, particularly at higher threshold probabilities. CONCLUSIONS NMP22 is a strong, independent predictor of bladder cancer in patients undergoing surveillance. Addition of NMP22 improves the accuracy of standard predictors by a statistically and clinically significant margin. Decision curve analysis suggests that integration of NMP22 into clinical decision-making helps spare unnecessary cystoscopies, with minimal increased risk of missing a bladder cancer recurrence. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e160 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eugene K. Cha New York, NY More articles by this author Christopher E. Barbieri New York, NY More articles by this author Michael Rink New York, NY More articles by this author Thomas F. Chromecki Graz, Austria More articles by this author Allison Dunning New York, NY More articles by this author Yair Lotan Dallas, TX More articles by this author Harun Fajkovic St. Poelten, Austria More articles by this author Douglas S. Scherr New York, NY More articles by this author Madhu Mazumdar New York, NY More articles by this author Shahrokh F. Shariat New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Nuclear Matrix Protein-22 and Telomerase Reverse Transcriptase Are Diagnostic Markers for Bladder Carcinoma in Egypt

Bladder carcinoma is the foremost oncologic problem among males in Egypt. Here, we evaluated the possible diagnostic value of the urinary Nuclear Matrix Protein-22 “NMP-22” and Telomerase Reverse Transcriptase “hTERT” among histological subtypes of bladder cancer. 120 males with non-muscle invasive bladder cancer, 21 non malignant bladder conditions and 21 healthy volunteers were included in this study. Estimation of hTERT and NMP-22 was done by PCR-ELISA and ELISA, respectively, from voided urine and results were compared to those of urine cytology. Results showed that urinary hTERT and NMP-22 were significantly higher in all cancer patients compared to control group. NMP-22 was able to discriminate between transitional cell bladder carcinoma “TCC” patients and squamous cell bladder carcinoma “SqCC” ones. Both markers succeded to discriminate between some transitional cell bladder carcinoma grades. Additionally, hTERT discriminated between some Tumor stages in both TCC and SqCC. Our results demonstrated that urinary hTERT and NMP-22 could be efficient urinary markers for the differential diagnosis of bladder cancer.

The Use of NMP22 and Urine Cytology for the Surveilance of Patients with Superficial Bladder Cancer

Aim To see if NMP22 combined with urine cytology can safely increase the interval between cystoscopies in the surveillance of superficial bladder cancers. Methods Thirty four patients with low grade superficial bladder transitional cell carcinomas were prospectively recruited and followed up with regular flexible cystoscopies over 2 years. Freshly voided urine was collected for urine cytology and NMP22 test prior to cystoscopy. Patients with suspicious cystoscopy findings or suspicious cytology underwent biopsies and/or resection of the suspicious lesions. Results 172 urine samples were collected and analyzed. The NMP 22 results were compared with voided urine cytology, cystoscopy and histological findings. Using the 10U/ml cutoff for quantitative measurement, the sensitivity, specificity, positive and negative predictive values of urinary NMP22 were 50%, 90.7%, 21.0%, and 97.3% respectively. When combined with voided urine cytology, the sensitivity, specificity, positive and negative predictive values were 71.4%, 88.5%, 25.0%, and 98.3% respectively. In comparison, the sensitivity, specificity, positive and negative predictive value of cystoscopy were 85.7%, 97.6%, 66.7%, and 99.2% respectively. Analysis with a receiver operating characteristic(ROC) curve found the ideal threshold of determinance of NMP22 for the detection of recurrences is 8.5U/ml with 100% sensitivity and 73.9% specificity. In our center, replacing alternate cystoscopy examination at 3,9,18 and 30 months with NMP22, results in a cost saving USD$740 or 37% per patient over 5 years. In the event of false positives, the patient will revert to the current surveillance schedule, with no increased costs incurred. Conclusion We propose that the optimal cutoff value for NMP22 is 8.5U/ml. At this level. the combination of the NMP22 BladderChek test and voided urine cytology is a sensitive non-invasive alternative to cystoscopy in the surveillance of patients who have had superficial low grade bladder cancer.

Combinations of urine-based tumour markers in bladder cancer surveillance

The aim of the study was to investigate whether combinations of urine-based tumour markers including urinary cytology (Cytology or Cyt) increase the sensitivity in the detection of bladder cancer recurrence. Urinary cytology, NMP22, UroVysion (FISH) and ImmunoCyt (uCyt+) were determined in 221 patients during the follow-up of non-muscle-invasive transitional cell carcinoma (NMI TCC) before cystoscopy (n = 49) or with the suspicion of TCC recurrence before transurethral resection of the bladder (n = 173). For all markers alone as well as in all possible combinations (multimarker panels, MPs) sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were evaluated. MPs were considered positive if at least one marker was positive. No malignancy was found in 108 patients, whereas recurrent TCC was confirmed in 113 patients. Sensitivity and specificity for Cytology were 84% and 62%, for NMP22 68% and 49%, for FISH 72% and 63%, and for uCyt+ 73% and 62%, respectively. The NPV was below 80% for all markers alone. Combinations of two and three markers increased the sensitivity as well as the NPV to over 90 and 80%, by reducing specificity to an average of 44% and 35%, respectively. The most sensitive combinations were NMP22, uCyt+ together with Cytology and FISH, and uCyt+ together with NMP22 (sensitivity for both combinations 98%). There was no further improvement when all four markers were combined. Combinations of tumour markers increased the sensitivity and NPV in the detection of recurrence of NMI TCC. A stepwise approach of tumour marker determination may be used to reduce the frequency of follow-up cystoscopies at a reasonable risk.

S2 Evaluation of the clinical value of urinary NMP22 as a marker in the surveillance of superficial transitional cell carcinoma of the urinary bladder

S2 Evaluation of the clinical value of urinary NMP22 as a marker in the surveillance of superficial transitional cell carcinoma of the urinary bladder

Expression and clinical significance of nuclear matrix protein 22 and cytokeratin 18 in transitional cell carcinoma of the bladder

To evaluate the expression and clinical significance of urinary nuclear matrix protein (NMP22) and cytokeratin 18 (CK18) for transitional cell carcinoma of the bladder. Urinary NMP22 and CK18 levels of 293 patients with transitional cell carcinoma of the bladder, 400 patients with non-transitional cell carcinoma of the bladder, and 105 bladder benign disease were analysed by enzyme-linked-immunosorbent assay (ELISA). The levels of urinary NMP22 and CK18 in the patients with transitional cell carcinoma of the bladder (M = 17.3 U/ml, M(CK18) = 484.2 U/L) were significantly higher than those in the non-transitional cell carcinoma of the bladder (M = 6.8 U/ml, M(CK18) = 156.0 U/L) and the benign disease group (M(NMP22) = 2.3 U/ml, M(CK18) = 66.6 U/L) (P < 0.001). The sensitivity and specificity of urinary NMP22 and CK18 were 79.2%, 88.6% and 78.2%, 82.9%, respectively, for transitional cell carcinoma of the bladder before any treatment. The joint sensitivity of the two markers was 91.7%. The NMP22 and CK18 levels were significantly lower in the recovered patients after surgical operation (P < 0.01), while in patients with recurrence or metastasis the levels of the markers were significantly higher (P < 0.01). There was a significant relationship between NMP22 and CK18, (r = 0.689, P < 0.01). The levels of urinary nmp22 and CK18 were significantly different among pathological grade G1, G2, G3, and stage Ta, T1, T2, T3 (P < 0.01). NMP22 and CK18 are useful tumor marker for diagnosis of transitional cell carcinoma of the bladder and for monitoring the state of illness. The joint use of the two markers can improve the sensitivity of cancer detection. NMP22 and CK18 may become a new class of tumor markers, and to be the basis for development of a new assay with an increased efficacy for the detection and treatment of bladder cancer.

Urinary insulin‐like growth factor 2 identifies the presence of urothelial carcinoma of the bladder

To examine urinary insulin-like growth factor 2 (IGF-2) levels in patient urine samples and determine the potential of IGF-2 as a marker for the presence of urothelial carcinoma of the bladder (UCB). The current gold standard for diagnosis of UCB is cystoscopy and cytological analysis. The identification of an accurate urine marker for UCB with the potential to replace unnecessary cystoscopy would benefit patients with UCB and others investigated after detecting haematuria. In the present study, we analysed 65 urine samples, and optimized an enzyme-linked immunosorbent assay-based approach to measure urinary levels of IGF-2. Based on a threshold of 5.4 ng/mL, patients with UCB have significantly elevated levels of urinary IGF-2 (P = 0.009) and this difference remained significant after adjustment for age and sex (P = 0.04). Sensitivity and specificity values of 80% and 52%, respectively, were determined for urinary IGF-2 alone and when combined with nuclear matrix protein 22 (NMP22; an approved biomarker for detection of UCB). There was a positive correlation between urinary IGF-2 levels and NMP22 levels in patient urine samples and the combined assay improved the detection of UCB (sensitivity 85% and specificity 52%). Substantiated evidence has identified IGF-2 as a valuable marker for UCB. In addition, the novel observations of the present study have shown that aberrant levels of IGF-2 occurring in the presence of UCB, can now be determined through a simple and inexpensive urine assay.

MP-2.26: Urinary NMP22 BladderChek Test in Diagnosis of Bladder Cancer and Comparison with Urinary Cytology and Cystoscopic Biopsy

MP-2.26: Urinary NMP22 BladderChek Test in Diagnosis of Bladder Cancer and Comparison with Urinary Cytology and Cystoscopic Biopsy

Urinary markers in screening patients with hematuria

Hematuria is a common presenting symptom of urothelial malignancy. Although conventional urine analysis is very sensitive in detecting the presence of hematuria, it is not specific in detecting bladder cancer or other urinary-tract cancers. The noninvasive urinary tests NMP22 and UroVysion have been approved by the U.S. Food and Drug Administration for bladder cancer screening. These tests have better sensitivity than cytology for detecting bladder cancer in patients who present with hematuria. The positive predictive values of both tests increase in individuals with hematuria who have risk factors for bladder cancer. Evaluating hematuria with sensitive markers, such as NMP22 and UroVysion, in high-risk populations offers an opportunity to develop effective strategies for bladder cancer screening.

Influencia del retraso en el procesamiento preanalítico de la orina en la determinación del NMP22

ObjectivesTo evaluate the influence of the delay in urinary nmp22 preanalytical processing. Material and methodsTwenty-eight voided urine samples were taken: bladder cancer (14), urine tract infections (4), lithiasis (4), healthy volunteers (1), and with other no malignant bladder diseases (5). All samples, were maintained at environment temperature, and were processed according to the stabilization of parts of urine collected at 0, 30, 90 and 150 minutes. Samples were stored at 4 °C until its determination. nmp22 was determined with the IMMULITE One analyzer. ResultsThere were no significant differences for nmp22 levels between each different point of time studied. ConclusionsDelay up to 2 hours and a half when we add stabilization solution to urine samples no affects nmp22 results. That thing, might provide more confidence and flexibility on quantitative immunoassays that required urine stabilization.

Surveillance for recurrent bladder cancer using a point-of-care proteomic assay: Grossman HB, Soloway M, Messing E, Katz G, Stein B, Kassabian V, Shen Y, Department of Urology, M.D. Anderson Cancer Center, Houston, TX

At least 50% of patients with a history of bladder cancer have recurrences, so rigorous surveillance is necessary. Cystoscopy is standard but can fail to detect some bladder cancers, so a urine test is frequently part of the evaluation. To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could improve detection of recurrence during monitoring of patients with a history of bladder cancer. From September 2001 to February 2002, 23 academic, private practice, and hospital facilities in 9 US states prospectively enrolled 668 consecutive patients with a history of bladder cancer in this cross-sectional study. Patients provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. Diagnosis of bladder cancer recurrence, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to detection. Testing for the NMP22 tumor marker was conducted in a blinded manner. Bladder cancer was diagnosed in 103 patients. Cystoscopy alone identified 91.3% of the cancers (94/103; 95% confidence interval [CI], 84.1%-95.9%). The combination of cystoscopy with the NMP22 assay detected 99.0% of the malignancies (102/103; 95% CI, 94.7%-100%; P = .005). The NMP22 assay detected 8 of 9 cancers that were not visualized during initial cystoscopy, including 7 that were high-grade. The sensitivity and specificity of the NMP22 test alone were 49.5% (51/103; 95% CI, 39.5%-59.5%) and 87.3% (493/565; 95% CI, 84.2%-89.9%), respectively. Voided cytology detected only 3 of the malignancies missed during initial cystoscopy and did not significantly increase the sensitivity of cystoscopy (94.2%; 95% CI, 87.7%-97.8%; P = .08). The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the ability to detect recurrent bladder cancer, with test results available during the patient visit.

Surveillance for Recurrent Bladder Cancer Using a Point-of-Care Proteomic Assay

At least 50% of patients with a history of bladder cancer have recurrences, so rigorous surveillance is necessary. Cystoscopy is standard but can fail to detect some bladder cancers, so a urine test is frequently part of the evaluation. To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could improve detection of recurrence during monitoring of patients with a history of bladder cancer. From September 2001 to February 2002, 23 academic, private practice, and hospital facilities in 9 US states prospectively enrolled 668 consecutive patients with a history of bladder cancer in this cross-sectional study. Patients provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. Diagnosis of bladder cancer recurrence, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to detection. Testing for the NMP22 tumor marker was conducted in a blinded manner. Bladder cancer was diagnosed in 103 patients. Cystoscopy alone identified 91.3% of the cancers (94/103; 95% confidence interval [CI], 84.1%-95.9%). The combination of cystoscopy with the NMP22 assay detected 99.0% of the malignancies (102/103; 95% CI, 94.7%-100%; P = .005). The NMP22 assay detected 8 of 9 cancers that were not visualized during initial cystoscopy, including 7 that were high-grade. The sensitivity and specificity of the NMP22 test alone were 49.5% (51/103; 95% CI, 39.5%-59.5%) and 87.3% (493/565; 95% CI, 84.2%-89.9%), respectively. Voided cytology detected only 3 of the malignancies missed during initial cystoscopy and did not significantly increase the sensitivity of cystoscopy (94.2%; 95% CI, 87.7%-97.8%; P = .08). The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the ability to detect recurrent bladder cancer, with test results available during the patient visit.

Urinary Survivin Test Compared to the Nuclear Matrix Protein (NMP)-22 Test and Urine Cytology for the Diagnosis of Bladder Cancer

Purpose: The aim of this study was to compare the sensitivity and specificity of the urinary survivin test for the diagnosis of bladder cancer with the nuclear matrix protein (NMP)-22 test and the urine cytology, and we wanted to correlate survivin with the tumor stage and grade. Materials and Methods: Between October 2002 and March 2004, voided urine samples were obtained from 41 patients with bladder cancer and also from 36 controls who had no evidence of bladder cancer. The urinary survivin and NMP-22 levels were measured using a DuoSet IC ELISA kit and an automated chemiluminescent assay system. The results were compared with the cytologic results and the pathologic findings. Results: The comparative results showed the higher sensitivity for the urinary survivin test (78.0%) and the NMP-22 test (75.6%) than for the urine cytology (65.8%) for the detection of bladder cancer. The specificity of urinary survivin (86.1%) and urine cytology (97.2%) were higher than that for the NMP-22 test (66.6%). Measuring the urinary survivin level was a more accurate test than the urinary NMP-22 test and the urine cytology for the detection of lower grade and superficial bladder cancer. Conclusions: The urinary survivin test was superior to urine cytology for sensitivity and specificity, and these two parameters of the urinary survivin test were higher than those of the NMP-22 test. Especially, the urinary survivin test is an accurate diagnostic test for superficial and lower grade bladder tumor. Our results suggested that the urinary survivin test appears to be a reliable diagnostic test to identify patients with bladder cancer. (Korean J Urol 2006;47:1041-1045) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

Urinary NMP22® BladderChek® Test in the Diagnosis of Superficial Bladder Cancer

ObjectiveTo study the diagnostic efficacy of the NMP22® BladderChek® test and to compare it to cytology in the detection of bladder cancer. MethodsWe evaluated 106 voided urinary specimens of patients with suspicion of bladder cancer. All voided urine samples were evaluated by the NMP22 BladderChek test, cytology, sediment and culture. The diagnostic value of the NMP22 BladderChek test was evaluated according to correlation with cystoscopic findings and, in case of tumour, histological findings. A negative test result in a pTaG1 tumour was not considered false-negative in this study. The results were compared to the diagnostic value of cytology. Moreover, the value of the combination of cytology and the NMP22 BladderChek test was determined. ResultsIn total, 29 patients had histologically proven transitional cell carcinoma of the bladder. The NMP22 BladderChek test detected 40% of 15 pTa tumours and 83.3% of the 6 pT1 tumours. Cytology detected pTa in 33.3% and pT1 in 66.6%. The 1 CIS lesion was detected by cytology. In the group of patients in follow-up the sensitivity and specificity were 57.1% (CI 28.8–82.3) and 89.8% (CI 79.2–96.2) for the NMP22 BladderChek test and 42.9% (CI 17.7–71.7) and 93.2% (CI 83.5–98.1) for cytology. ConclusionThe NMP22 BladderChek test has a slightly higher sensitivity compared to cytology, without a relevant loss in specificity. Furthermore it is an easy test with instant result. However, no extra tumours were detected by adjunction of the NMP22 BladderChek test.