Nuclear Matrix Protein 22 Test Research Articles

An ensemble approach of urine sediment image analysis and NMP22 test for detection of bladder cancer cells.

BackgroundBladder cancer is the eighth most common cancer and the second most common urological cancer in Korean males. Current diagnostic tools for bladder cancer include cystoscopy (an upper tract study), urine cytology, and nuclear matrix protein 22 (NMP22) test. In this study, we evaluated the detection rate of atypical/malignant urothelial cells in urinary sediment images when flagged for positive NMP22 test.MethodsNMP22 was measured by NMP22 BladderChek Test (Abbott Laboratories) and urine chemical and sediment analysis were performed by fully automated cobas 6500 urine analyzer (Roche Diagnostics). Specimens that met the manual microscopic examination (MME) criteria were then subjected to an on‐screen review of images. We subsequently reviewed sediment images and examined under the microscopy for the flagged cases.ResultsOf the 1217 patients, 345 (28.3%) had positive NMP22 results, whereas 872 (71.7%) had negative results. Out of the positive results, 154 (12.7%) were positive and 191 (15.7%) weakly positive for NMP22. Screened review of flagged specimens (ie, positive NMP22 result) with sediment imaging analysis revealed that suspicious urothelial carcinoma cells were detected in only two cases (0.8%). In the NMP22 negative flagged cases, the suspicious neoplastic cells were not found.ConclusionsOur findings suggest that the NMP22 test should be added to the flagging criteria for MME to improve diagnostic accuracy. The combination of urine sediment imaging analysis and NMP22 test can significantly assist technicians in the review of specimens.

Clinical evaluation of nuclear matrix protein 22 as urinary marker of transitional cell carcinoma of bladder

OBJECTIVES. Biomarkers (BTA, NMP22, FDP etc.) have been and continue to be evaluated as adjuncts or substitutes for cystoscopy, which is invasive and uncomfortable for some patients. Nuclear matrix protein-22 (NMP22) is involved in the regulation of nuclear processes. The main objective of the present study is to evaluate the clinical utility of urinary NMP22 as a tumor marker in the follow-up of transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS. The study included 62 patients undergoing follow-up, who had had TCC of bladder but who were disease-free at the beginning of the study, as confirmed by cystoscopy. Urine samples were collected for urinary cytology and NMP22 test before the cystoscopy. All samples were processed according to the instructions provided with the manufacturer's kit instructions. Results. 12 cases of TCC recurrences were detected with biopsy. Cystoscopy was positive in 8 cases, NMP22 test was positive in 11 cases, and in only one case the cytopathology yielded positive results. In 14 cases NMP22 resulted as false positive. CONCLUSIONS. Urinary NMP22 appeared to be a potential tumor marker for detecting TCC of the bladder, which might rise the sensitivity of cystoscopy especially in high-grade cancer surveillance more than cytology might do.

Urinary UBC Rapid and NMP22 Test for Bladder Cancer Surveillance in Comparison to Urinary Cytology: Results from a Prospective Single-Center Study.

Background: Non-muscle invasive bladder cancer (NMIBC) is associated with high rates of recurrence, resulting in frequent follow-up cystoscopies. We evaluated the use of two point-of-care tests - the nuclear matrix protein 22 (NMP22) and urinary bladder cancer antigen (UBC) Rapid - compared to routine follow-up in patients with a previous history of NMIBC.Methods: 31 patients with cystoscopy-verified active bladder cancer, and 44 follow-up patients without disease as confirmed by cystoscopy were prospectively enrolled. All urine samples were analyzed by voided urine and bladder washing cytology, NMP22 and UBC rapid test (qualitatively and quantitatively). The best cutoff (highest Youden index; ≥6.7 ng/ml) for the quantitative UBC was determined by receiver operating characteristic curves.Results: Voided urine and barbotage cytology resulted in a sensitivity of 25.8% and 32.3%, and a specificity of 100% and 100%, while the NMP22 showed a sensitivity and specificity of 12.9% and 100%, respectively. The qualitative and quantitative UBC Rapid revealed a sensitivity of 61.3% and 64.5%, with a specificity of 77.3% and 81.8%. Barbotage cytology and qualitative UBC test proved to be the best dual combination with the highest overall sensitivity (77.4%). In contrast to barbotage cytology alone, sensitivity increased from 21.4% to 50% for detecting low-grade tumors, and from 43.8% to 100% for high-grade cancers, but reducing specificity from 100% to 77.3%.Conclusion: Compared to urinary cytology, UBC tests alone as well as UBC tests in combination with bladder washing cytology revealed higher sensitivities in detecting low- and high-grade tumors, but at the expense of a lower specificity. Thus, currently cystoscopy cannot be replaced by any of the evaluated methods.

Long‐term outcomes in a high‐risk bladder cancer screening cohort

To evaluate the long-term outcomes in patients at high risk of bladder cancer who participated in a bladder cancer screening trial. Patients who were classified as high risk based on age ≥50years, ≥10 pack-years (combination of packs of tobacco per day and years of smoking) smoking and/or ≥15years environmental exposure were enrolled in a one-time screening trial using a nuclear matrix protein 22 (NMP22) assay, between March 2006 and November 2007, at Dallas Veterans Affairs Hospital. We assessed the subsequent detection of smoking-related malignancies (bladder, lung and renal cell carcinoma [RCC]) in these patients up until 31 January 2014. Multivariable regression analysis was used to determine factors associated with bladder cancer diagnosis and survival. The study cohort included 925 patients, of whom 886 (95.8%) were smokers and 613 (66.3%) had received hazardous occupational exposure. At initial screening, 57 patients had a positive NMP22 test and two had bladder cancer. Another nine patients (1.0%) were diagnosed with bladder cancer during the median follow-up of 78.4months. The bladder cancers were non-invasive (Ta) and seven were low grade and four high grade. RCC and lung cancer were diagnosed in 10 (1.1%) and 18 patients (1.9%), respectively. A total of 134 patients died, including three from RCC and 12 from lung cancer, but none from bladder cancer. Factors associated with worse overall survival on multivariable analysis were: lung cancer (hazard ratio [HR] 5.06; P < 0.001), microscopic or gross haematuria (HR 1.66; P = 0.006 and HR 2.11; P = 0.02, respectively), and >60 pack-years smoking history (HR 4.51; P = 0.037). At 6.5years of follow-up, no patients in this high-risk cohort developed muscle-invasive bladder cancer. Lung cancer, haematuria and >60 pack-years smoking history are independent predictors of mortality. Other-cause mortality is an important consideration in patients undergoing bladder cancer screening.

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

In this study, we investigated the efficacy of nuclear matrix protein 22 (NMP22) in the diagnosis and surveillance of bladder cancer. Patients with hematuria or who applied for cystoscopic control of proven bladder cancer were prospectively enrolled in this study. Routine cytologic examination and NMP22 test were performed on the voided urine sample obtained before the cystoscopy. The patients who had been diagnosed with bladder cancer were categorized according to stage, grade, number, size of the tumor and risk of the disease. Then the diagnostic performance of the NMP22 and the cytology test, alone or in combination, were evaluated separately using ROC curves in the diagnosis and surveillance groups. A total of 87 patients (87/136) were investigated because of hematuria. The sensitivity, specificity, positive and, negative predictive values, and positive likelihood ratio (LR+) of the NMP22 test were 70, 80, 68, 81, and 3.42%, respectively. While, the sensitivity, specificity, positive and, negative predictive values, and positive likelihood ratio (LR+) of the cytology examination were 27, 96, 82, 68, and 7.36%, respectively. There were 49 patients in the bladder cancer group. The sensitivity, specificity, positive, and negative predictive values and positive likelihood ratio (LR+) of the NMP22 test in these patients were 33, 76, 31, 78 and 1.37%, respectively. The sensitivity, specificity, positive and, negative predictive values, and positive likelihood ratio (LR+) of the cytology examination were 25%, 97%, 75%, 80% and 9.25, respectively. NMP22 test can be used as an adjunctive tool for the detection of bladder cancer, but its diagnostic performance is limited in surveillance when used alone or in combination with a cytology examination.

Overestimation of Nuclear Matrix Protein 22 in Concentrated Urine

To confirm the hypothesis that nuclear matrix protein 22 (NMP22) is overestimated in concentrated urine, we compared the NMP22 values measured at different dietary states. We retrospectively reviewed 531 healthy subjects who had had abnormal urinary NMP22 values ≥ 10 U/mL at the first test and underwent a second NMP22 test within 2 weeks. The first NMP22 test was performed after overnight fasting, and the second was performed with no dietary restrictions. We compared the NMP22 values between the 2 measurements and investigated the relationship between the NMP22 value and urine specific gravity. At the second test, 504 subjects (94.9%) had a normal NMP22 value of <10 U/mL and only 27 subjects (5.1%) persistently had an abnormal NMP22 value of ≥ 10 U/mL. Both NMP22 and urine specific gravity at the first test were significantly higher than at the second test (P <.0001). Subjects with an abnormal NMP22 value tended to have a more concentrated urine with a greater urine specific gravity than did the subjects with a normal NMP22 value. This difference was significant in the subgroup undergoing bowel preparation for colonoscopy (P <.001). NMP22 will be overestimated in concentrated urine after overnight fasting. When interpreting the NMP22 value, we should consider the overestimation of NMP22 in concentrated urine.

The Clinical Usefulness of Nuclear Matrix Protein-22 in Patients with End-Stage Renal Disease and Microscopic Hematuria

Objectives: To evaluate the sensitivity, specificity, and false-positive rate of the nuclear matrix protein-22 (NMP22) test in patients with end-stage renal disease (ESRD) and microscopic hematuria in order to avoid unnecessary follow-up tests for patients with false-positive NMP22 test results. Patients and Methods: Patients with ESRD were screened for microscopic hematuria as part of the pre-transplant workup. Patients with documented microscopic hematuria underwent workup as recommended by the American Urological Association. Results: Between January 2006 and April 2012, 277 patients with ESRD were referred to the Department of Urology for pre-transplant evaluation. Fifty-seven (22.6%) patients were found to have microscopic hematuria and underwent further testing. Nineteen (33.3%) patients demonstrated a positive NMP22 test result and 38 (66.7%) had a negative NMP22 test result. The false-positive rate was 32.7%. The sensitivity and specificity of the NMP22 test in this patient population were 50% and 67%, respectively. The positive predictive value of the test was 52.6% and the negative predictive value 97.3%. Especially noteworthy, the two detected transitional cell cancers of the urinary bladder were both demonstrated during cystoscopy, independent of their NMP22 or urine cytology test result. Conclusions: Our study revealed a significantly increased NMP22 test false-positive rate, low sensitivity, and specificity in the setting of high prevalence of microscopic hematuria, proteinuria, and low glomerular filtration rate in patients with ESRD. Therefore, cystoscopy remains the gold standard for patients with ESRD and microscopic hematuria for pre-transplant evaluation.

Influence of Urinary Tract Instrumentation and Inflammation on the Performance of Urine Markers for the Detection of Bladder Cancer

To evaluate the impact of inflammation and sampling on cytology, immunocytology, and fluorescence in situ hybridization (FISH) in comparison with NMP22 in hematuria patients. The specificity of urine markers for urothelial cancer is subject to exogenous factors. There is evidence that nuclear matrix protein 22 (NMP22) is influenced by urinary tract infection and instrumented urinary sampling (IUS). Samples from 1386 patients with histologic work-up were included. Cytology, immunocytology, FISH, and NMP22-enzyme-linked immunosorbent assay were performed. The presence of inflammation was evaluated by microscopy. The method of urine sampling was recorded in all cases. Any type of urinary tract manipulation was considered as IUS. False-positive results were compared with regard to the presence or absence of inflammation and mechanical manipulation. In all, 1050 (75.7%) patients had no evidence of urothelial cancer. NMP22 results were false positive in 74.3% and 38.4% of patients with and without IUS (P < .0001). False-positive test rates of cytology, immunocytology, and FISH were not increased after manipulation. Inflammation led to a rise in false-positive NMP22 test results (85.3% vs 61.4%, P < .0001). The presence of inflammation did not change the rate of false-positive cytology, immunocytology, and FISH results. This is the first study to investigate the impact of inflammation and IUS on cell-based urine markers. In contrast to the protein test NMP22, these factors did not impair the performance of cell-based tests. Hence, patients with positive cytology, immunocytology, and FISH results should undergo diagnostic work-up, even in the case of concomitant inflammation or IUS.

In the cystoscopic follow-up of non-muscle-invasive transitional cell carcinoma, NMP-22 works for high grades, but unreliable in low grades and upper urinary tract tumors

Two percent of the bladder non-muscle-invasive (NMI) transitional cell carcinomas (TCC) are associated with upper urinary tract (UUT) TCC. We evaluated the role of nuclear matrix protein-22 (NMP-22) (BladderChek) test in the diagnosis of lower urinary tract and UUT-TCC. From March 2009 to June 2011, 122 patients with bladder NMI-TCC underwent 205 control cystoscopy. A total of 95 (78 men and 17 women, mean age 60.7 years, range, 27-88) patients who were followed regularly with NMP-22 test and with follow-up cystoscopies (145 episodes; min. 1-max. 5) were included in this study. For routine monitoring of the UUT, IVU or CT urography was used once a year for high grades (HG), and once in every other year for low grades (LG). The sensitivity and specificity of NMP-22 were evaluated by ROC curves, and sensitivity, specificity, and positive and negative predictive values were calculated. Chi-square test was used for the differences between the subgroups. Cystoscopy and NMP-22 results of the patients included in the study revealed the sensitivity (44.4%) of the test was very low and the specificity (98.4%) was quite high (p < 0.001). Among the 10 cystoscopies where NMP-22 was negative, but cystoscopy was positive for tumor, 8 had LG and 2 had HG TCC. NMP-22 was never positive in low-grade tumors, in other words, all of the NMP-22-positive 8 tumors were high grade. On the other hand, in 20% (2/10) of the cases, NMP-22 can be negative although the tumor was high grade. Two (2.1%) HG UUT-TCC were detected in 95 patients. These 2 patients were within the 125 cystoscopies (75 patients) where both NMP-22 and cystoscopy were negative for tumor. Nuclear matrix protein-22 cannot detect LG TCC. However, it detects overwhelming majority of HG TCC. For this reason, positive NMP-22 test largely indicates HG TCC. NMP-22 is also not reliable in UUT-TCC, even in HG tumors.

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

What's known on the subject? and What does the study add? The prognosis of bladder cancer significantly 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 specificity 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. 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. 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 findings. Histopathological analysis found three papillary urothelial neoplasms of low malignant potential, five 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%, specificity 28.57%; negative predictive value 99.04%, positive predictive value 12.24%). Gross haematuria affected NMP22 results (odd ratio [OR] 3.49, 95% confidence interval [CI] 1.81-6.73). Infection also affected NMP22 results (OR 4.13, 95% CI 2.31-7.35). NMP22 was more frequently positive in urine with creatinine concentration >2.5 g/L (OR 1.61, 95% CI 0.91-2.86). 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.

Diagnostic Value of the Nuclear Matrix Protein 22 Test and Urine Cytology in Upper Tract Urothelial Tumors

Objective: To investigate the diagnostic value of the nuclear matrix protein 22 (NMP22) test in comparison to urine cytology for the detection of upper tract urothelial carcinoma. Patients and Methods: Patients with transitional cell carcinoma of the upper urinary tract (n = 34) and patients with renal calculosis (n = 25) were included in this study. Voided urine samples and separated catheter urine specimens were assayed for NMP22 and cytological examination. Results: The sensitivity of the NMP22 test in separated and voided urine was 73.2 and 70.5%, respectively, compared to 64.7 and 58.8% of urine cytology. The specificity of the NMP22 test in separated and voided urine was 88 and 92%, respectively, compared to 96 and 96% of urine cytology. The combination of separated and voided urine is the best method because the sensitivity is 79.41% and specificity 88%. There is a high agreement of the NMP22 test in voided and separated urine (kappa = 0.795, p < 0.01), indicating that the voided urine is adequate for diagnosis. Conclusions: The NMP22 test has higher sensitivity but lower specificity than cytology. The combination of these two tests could be a very useful diagnostic method for detection of upper urothelial tumors.

Comparison of the sensitivity and specificity of urine cytology, urinary nuclear matrix protein-22 and multitarget fluorescence in situ hybridization assay in the detection of bladder cancer

This study aimed to compare the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of urine cytology, BladderChek® nuclear matrix protein-22 (NMP22) and UroVysion™ fluorescence in situ hybridization (FISH) tests in patients with newly diagnosed bladder cancer, those with recurrent bladder cancer, and those with bladder cancer but in remission during surveillance. Voided urine samples obtained from 178 patients with suspected or known bladder cancer about to undergo diagnostic or surveillance cystoscopy and 25 control subjects without the disease were divided into four and used for urine culture and cytology, NMP22 BladderChek and UroVysion FISH tests. The sensitivity, specificity, PPV and NPV for each test were calculated. Comparison was made between the ability of each test to detect bladder cancer in the three category of patients listed. Of the 178 patients with bladder cancer, 43 were newly diagnosed, 58 had recurrent disease and 77 were in remission. The sensitivity of each test in newly diagnosed patients was: urine cytology 28%, NMP22 88% and FISH 80%; and in patients with recurrent disease: urine cytology 33%, NMP22 57% and FISH 85%. The mean specificity for urine cytology, NMP22 and FISH was 95%, 67% and 48%, respectively. Of the tests used in the study for detection of bladder cancer, NMP22 appeared to be most cost-effective and rapid, with relatively high sensitivity and specificity in all categories of patients. The NMP22 test may be considered a new gold standard for the assessment of patients with known or suspected bladder cancer.

Impact of clinical factors, including a point‐of‐care nuclear matrix protein‐22 assay and cytology, on bladder cancer detection

To determine whether the nuclear matrix protein-22 (NMP22) assay can improve the accuracy of discriminating between high-risk patients with and without bladder cancer. Age, gender, race, smoking status, haematuria and its extent, and the NMP22 and urinary cytology results, were available for 1272 patients. The data of 670 (52.7%) from four study sites were used to develop a logistic regression model-based nomogram to predict the presence of bladder cancer. The remaining data from 602 (47.3%) patients from nine study sites were used to externally validate the nomogram. A separate nomogram was developed for urinary cytology, and for the combination of NMP22 and urinary cytology findings. Of 1272 patients, 76 (6.0%) had bladder cancer, 217 (17.1%) were NMP22-positive and 17 (1.3%) had malignant cells on urinary cytology. NMP22 and urinary cytology results were independent predictors of bladder cancer (P = 0.005 and 0.007, respectively). In external validation, the area under the curve (AUC) for NMP22 was 76.0% vs 56.2% for cytology. External validation of the multivariable NMP22-based bladder cancer nomogram gave an AUC of 82.4% vs 74.7% for the multivariable cytology-based nomogram (gain 7.7%; P = 0.006) vs 82.6% for the multivariable nomogram combining NMP22 and cytology results (gain 0.2%; P = 0.1). The ability of the NMP22 test to predict bladder cancer in high-risk patients significantly exceeds that of urinary cytology. The NMP22-based nomogram can help to identify individuals at risk of bladder cancer.

Early results of bladder‐cancer screening in a high‐risk population of heavy smokers

To report first results of an early bladder-cancer detection programme, and to evaluate the detection rate and the diagnostic value of the tests used. Urine samples of 183 screened subjects with a history of smoking of > or =40 pack-years were collected for analysis with a urinary dipstick test for haematuria, the nuclear matrix protein-22 test (BladderChek, Matritech, Inc., Newton, MA, USA), voided urine cytology and a molecular cytology test (UroVysion, Abbott Molecular Inc., Des Plaines, IL, USA). Participants with at least one positive test result had a further evaluation including cystoscopy and radiological imaging. The subjects' risk factors, test results and histological findings were analysed. In all, 75 subjects had at least one positive test result and were evaluated further; abnormal histological findings were detected in 18 (24% of those who had cystoscopy, 9.8% of the original 183), 15 of those in the urinary bladder, with pTaG1 (one), carcinoma in situ (two), dysplastic lesions (11) and one an inverted papilloma. In the upper urinary tract, two urothelial tumours (pTaG1 and pTxN2G3) and one renal cell carcinoma (pT1G2) were detected by computed tomography. In summary, six of 183 subjects (3.3%) had a histologically confirmed malignant tumour and another 12 (6.6%) were identified with a possible pre-cancerous lesion of the urinary tract. The urinary dipstick, BladderChek, cytology and UroVysion detected (i.e. were true-positive in) nine (50%), one (6%), seven (39%) and 11 (61%) of the 18 tumours found, while they failed to detect nine (50%), 17 (94%), 11 (61%) and seven (39%) of these lesions, respectively. Omitting the urine dipstick test, the BladderChek, cytology or UroVysion from the test setting could have spared 40, five, two or one subjects(s) from unnecessary invasive interventions; however, three, none, two or six lesions, would have been missed. More positive screening tests per subject was associated with a higher probability of a (pre)-malignant lesion. Screening a high-risk group with a history of smoking of > or =40 pack-years showed a significant proportion (3.3%) with malignancy. These first results are encouraging and warrant continuation of the screening programme. In this series the most efficient screening tool was the combination of UroVysion, cytology and urinary dipstick testing. Of special scientific interest will be the follow-up of those patients with a possible pre-cancerous lesion.

Urinary cytology and nuclear matrix protein 22 in the detection of bladder cancer recurrence other than transitional cell carcinoma

To assess the value of nuclear matrix protein-22 (NMP22), compared with urinary cytology, in predicting the recurrence of bladder cancer that is not transitional cell carcinoma (non-TCC). We tested the sensitivity, specificity and the predictive accuracy of NMP22 in the context of non-TCC bladder cancer recurrence, and compared it to the performance of urinary cytology. The study group comprised 2687 patients with history of non-muscle-invasive bladder cancer from 10 centres across four continents. The mean patient age was 64.8 years and 75.4% were men; of all patients, 513 (19.1%) had positive urinary cytology, 906 (33.7%) had a positive NMP22 test (>or=10 units/mL) and 80 (3.0%) had non-TCC recurrence. Most of these, i.e. 60 (75%), were stage >or=T2. The sensitivity and specificity of urinary cytology were, respectively, 20.0% and 94.8%, vs 77.5% and 81.8% for NMP22 of >or=10 units/mL. The predictive accuracy of urinary cytology was 57.5%, vs 87.1% for NMP22 >or= 10 units/mL. A combined model that included dichotomized NMP22 and urinary cytology was 85.3% accurate. The ability of a NMP22 level of >or=10 units/mL to predict non-TCC recurrence was better than that of urinary cytology, suggesting that NMP22 might have a role in the surveillance of patients at risk of non-TCC recurrence.

Clinical evaluation of nuclear matrix protein 22 as urinary marker of transitional cell carcinoma of bladder

Objectives. Biomarkers (BTA, NMP22, FDP etc.) have been and continue to be evaluated as adjuncts or substitutes for cystoscopy, which is invasive and uncomfortable for some patients. Nuclear matrix protein-22 (NMP22) is involved in the regulation of nuclear processes. The main objective of the present study is to evaluate the clinical utility of urinary NMP22 as a tumor marker in the follow-up of transitional cell carcinoma (TCC) of the bladder. Materials and Methods. The study included 62 patients undergoing follow-up, who had had TCC of bladder but who were disease-free at the beginning of the study, as confirmed by cystoscopy. Urine samples were collected for urinary cytology and NMP22 test before the cystoscopy. All samples were processed according to the instructions provided with the manufacturer's kit instructions. Results. 12 cases of TCC recurrences were detected with biopsy. Cystoscopy was positive in 8 cases, NMP22 test was positive in 11 cases, and in only one case the cytopathology yielded positive results. In 14 cases NMP22 resulted as false positive. Conclusions. Urinary NMP22 appeared to be a potential tumor marker for detecting TCC of the bladder, which might rise the sensitivity of cystoscopy especially in high-grade cancer surveillance more than cytology might do.

Urinary nuclear matrix protein 22 for diagnosis of renal cell carcinoma

To determine the incidence of positive urinary nuclear matrix protein 22 (NMP22) values, which are currently used to detect transitional cell carcinoma of the bladder, in renal cell carcinoma (RCC). Urinary NMP22 values were determined preoperatively in 41 patients in whom a solid renal mass had been detected using CT and who were scheduled for radical nephrectomy; 38 of these patients were diagnosed with RCC. Two patients had xanthogranulomatous pyelonephritis and one had metastasis of a small cell adenocarcinoma to the kidney; these patients were excluded from the study. A total of 30 patients with kidney stones and simple renal cysts were used as controls. The urinary NMP22 values of the RCC patients were significantly higher than those of the controls. Of the 38 patients with RCC, 23 (60.5%) had positive urinary NMP22 values > or =10 U/ml. There were four measurements above this cut-off level in the control group. Urinary NMP22 values increased with an increase in pathologic tumor stage, but the correlation was not statistically significant. There was no correlation between grade and urinary NMP22 or between tumor burden and urinary NMP22. The urinary NMP22 test may help to diagnose RCC and may also result in an increase in the incidental discovery of RCC. As elevated urinary NMP22 levels have also been found to occur in RCC, patients with suspected bladder cancer and positive urinary NMP22 levels should be more broadly evaluated. Specific NMP assays for renal tumor cells may increase the utility of the test for RCC.

Evaluation of nuclear matrix protein 22 (NMP22) as a tumor marker in the detection of bladder cancer.

We prospectively evaluated the performance of urinary NMP22 test in the detection of transitional carcinoma (TCC) of the bladder. Urine samples were obtained from 39 patients with known bladder cancer, 37 patients with primary hematuria. 18 with benign urological conditions and 20 healthy subjects. Overall sensitivity and specificity of NMP22 with reference value of 10 U/ml was 72 and 73%, respectively. Sensitivity for pT1 and pT2 tumors was 83%, whereas that for pTa tumors was 55%. When the test was determined before and after transurethral resection (TUR) of bladder tumor, it was shown that the TUR effected the NMP22 level. Urinary NMP22 was highly sensitive for high-risk bladder cancer. However, the sensitivity of the test is somewhat lower in low grade and stage tumors. Additionally, the effect of previous resection limits its value in the follow up of patients with superficial tumors. The larger series with longer follow up may lead us to determine the time to neglect the effect of TUR on NMP22 and the test kit should be upgraded by the manufacturer to exclude the false positive results due to inflammatory conditions.

Comparison of the monoclonal UBC-ELISA test and the NMP22 ELISA test for the detection of urothelial cell carcinoma of the bladder

Objectives. To compare the diagnostic value of two enzyme-linked immunosorbent assay (ELISA) tests, the nuclear matrix protein 22 (NMP22) test and a newly developed urinary bladder cancer (UBC) test, in patients having symptoms suggestive of urothelial cell carcinoma (UCC) and patients under follow-up after transurethral resection (TUR). Methods. Two hundred forty patients with a mean age of 65.8 years (range 22 to 92) were included in this retrospective study. The tests were performed on previously frozen urine samples. Eighty-one patients had symptoms suggestive of bladder cancer and 159 patients were being followed up after complete TUR of UCC. Voided urine was evaluated by the NMP22 test and the monoclonal UBC-ELISA test, which traces cytokeratins 8 and 18. All patients underwent subsequent cystoscopy and biopsy evaluation of any suspicious lesion. The cutoff levels for bladder cancer positivity were 10 U/mL for the NMP22 test and 12 μg/L for the UBC test. Results. In the 54 patients with histologically proved UCC, the NMP22 test had a sensitivity of 55.5% and the UBC test a sensitivity of 64.8%. According to the histologic stages, the sensitivity of NMP22 was 51.7% in pTa tumors, 46.1% in pT1, and 70% in pT2 or higher tumors; the sensitivity of UBC was 62.1% in pTa, 53.8% in pT1, and 80% in pT2 or higher tumors. For histologic grades 1 to 3, the sensitivity was 50%, 50%, and 68.7% for NMP22 and 66.6%, 60%, and 68.7% for UBC, respectively. The specificity was 79% and 92% for NMP22 and UBC, respectively. Conclusions. The monoclonal UBC-ELISA test is superior to the NMP22 test in both sensitivity and specificity. Nevertheless, neither test can replace cystoscopy.

Comparison of the Nuclear Matrix Protein 22 with Voided Urine Cytology and BTA stat Test in the Diagnosis of Transitional Cell Carcinoma of the Bladder

Objective: To assess sensitivity, specificity, accuracy, positive predictive value and negative predictive value of nuclear matrix protein 22 (NMP22) test, BTA stat test and cytology in the urine of patients with a spectrum of urologic conditions, including bladder cancer. Methods: A total of 140 patients (40 with bladder cancer) provided a urine sample which was divided into appropriate aliquots for each of the tests cited above. The endoscopist, pathologist, cytologist and the person performing BTA stat test and NMP22 test were blinded as to the results of the other tests. Results: Receiver-operating characteristics curve interpretation determined that 12.0 U/ml was an optimal reference value for NMP22 to detect transitional cell carcinoma of the bladder in this patient group. Comparative results demonstrate a clear superiority of NMP22 and BTA stat tests in sensitivity in bladder cancer detection (p < 0.01), while cytology and NMP22 were better than BTA stat test in specificity (p < 0.05). Conclusions: NMP22 and BTA stat test results represented significant improvement over urinary cytology for detection of transitional cell carcinoma. The sensitivities of NMP22 and BTA stat tests for detection of transitional cell carcinoma in this group of patients were as much as twice that of cytology. When the cutoff value of urinary NMP22 was set at 12.0 U/ml, NMP22 was more accurate than the other tests (p < 0.05).