Urinary Nuclear Matrix Protein Research Articles

Changes in Urinary Exosomal Nuclear Matrix Protein-22 in Dogs With Urothelial Carcinoma: A Pilot Study.

Nuclear matrix protein-22 (NMP-22) is widely used in human medicine as a prognostic and diagnostic tool for urothelial carcinoma (UC). In addition, the use of urinary exosomes as a liquid biopsy tool is emerging for the diagnosis of certain types of cancer in human medicine. This study aimed to investigate the change in urinary exosomal NMP-22 for the diagnosis of UC in dogs. Among canine patients who visited the veterinary hospital, urine was collected from those whose owners provided consent. A total of 23 dogs (UC group, n=6; control group, n=17) were included in the analysis. After exosomes were isolated from the urine, NMP-22 was measured using enzyme-linked immunosorbent assay. In the UC group, the expression of NMP-22 in urinary exosomes was significantly higher than that in non-UC groups (p<0.0001). NMP-22 is significantly increased in exosomes in the urine of dogs diagnosed with UC, suggesting that urinary exosome NMP-22 can be considered as one of the liquid biopsy tools for diagnosing UC in dogs.

To Determine The Diagnostic Accuracy of Urinary Nuclear Matrix Protein 22 in Detection of Recurrence of TCC Bladder Among Patients Who Are on Active Surveillance By Taking Cystoscopic Biopsy As A Gold Standard

Objective: To determine the diagnostic accuracy of urinary nuclear matrix protein 22 in detection of recurrence of TCC bladder among patients who are on active surveillance by taking cystoscopic biopsy as a gold standard.&#x0D; Study Design: Cross-sectional study.Place and Duration of Study: Departments of Urology, Histopathology and Molecular Biology: Sindh Institute of Urology and Transplantation (SIUT), Karachi Pakistan, from Jan 2021 to Jun 2021.&#x0D; Methodology: Total 83 patients previously biopsy proven bladder carcinoma who are on active surveillance whether or not they have received intravesical chemotherapy were included in this study. All the information were noted into proforma, &#x0D; Results: The average age of the patients was 48.80±11.86 years. There were 46(55.42%) male and 37(44.58%) female. Sensitivity, specificity, PPV, NPV and accuracy of urinary nuclear matrix protein 22 was 88.9%, 80%, 93.3%, 69.6% and 86.7% resepctively.Practical implication: This study will help us to diagnose TCC bladder in early stages and to manage it in time sothat morbidity and mortality may be reduced.&#x0D; Conclusion: Measuring NMP22 level in the blood is a very important tool for detecting Tcc of the urinary bladder as it is much specific and sensitive test.

Iodide-Enhanced Perovskite Nanozyme-Based Colorimetric Platform for Detection of Urinary Nuclear Matrix Protein 22.

In the last decade, perovskite nanocrystals (PNCs) have brought extensive thinking owing to their excellent optical properties. Recently, we have uncovered the peroxidase-like activity of PNCs and used this for detecting many small molecules; however, the low enzymatic activity makes them unsuitable for fluorescence analysis, which is easily disturbed by the autofluorescence of biological media. This greatly limits their application in bioanalysis. Thus, the development of a method to facilely modulate the activity of PNCs for the instrument-free colorimetric detection is highly desirable. Herein, we demonstrated an iodide-enhanced perovskite nanozyme-based colorimetric platform for the visual assay of urinary nuclear matrix protein 22 (NMP22), a typical biomarker for the diagnosis of bladder cancer. We discovered that halogen could regulate the activity of perovskite nanozymes through a simple anion replacement reaction. Experimental analysis suggested that CsPbI3 nanocrystals (NCs) displayed 24-fold higher catalytic efficiency than classical CsPbBr3 NCs. As a proof-of-concept assay, the CsPbI3 NCs could be explored into an immunoassay for the detection of NMP22 in clinical urine specimens, resulting in a low detection limit of 0.03 U/mL. This iodide-enhanced immunoassay deepens our understanding of perovskite nanozymes and also provides great potential for bioanalysis.

Clinical value of urine nuclear matrix protein 22 (NMP22) quantitative test in the diagnosis of bladder cancer in a schistosoma endemic region

Background: Bladder cancer is the ninth commonest cancer and the 13th most common cause of mortality worldwide. Its early diagnosis poses a great challenge therefore the need to identify biomarkers which may improve the current diagnostic practice.Methods: This is a prospective study of patients managed for bladder cancer at the urology unit, department of surgery, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria between April 2019 to June 2020. Urine cytology, urine nuclear matrix protein 22 (NMP22) quantitative test and histology of the bladder biopsy specimens were done at the Histopathology and Chemical Pathology laboratory respectively of the Usmanu Danfodiyo University Teaching Hospital, Sokoto. Data was collected using a structured proforma and analyzed using statistical package for social sciences (SPSS) version 20.0.Results: Eighty-three patients enrolled in the study however 46 of them with features of bladder carcinoma participating in the study group and 37 in the control group. The study and control groups' mean age and age range are (49.70±11.45,18-69) and (51.84±13.75,18-78) years, respectively. The sensitivity, specificity, PPV, NPV and AUC of urine NMP22 and urine cytology in the study were (78.3% vs. 58.7%), (32.4% vs. 100.0%), (59.0% vs. 100.0%), (54.6% vs. 66.1%), (0.207 vs. 0.538) respectively for the diagnosis of bladder cancer.Conclusions: Urine NMP22 quantitative test shows high sensitivity, low specificity and a low AUC compared to urine cytology and thus of poor clinical value in the diagnosis of bladder cancer in our region.

Clinical evaluation of urine laminin-γ2 monomer as a potent biomarker for non-muscle invasive bladder cancer.

To evaluate whether urine laminin-γ2 monomer (Ln-γ2m) offers a useful biomarker for patients with non-muscle-invasive bladder cancer (NMIBC). Participants comprised 297 patients, including 111 patients with NMIBC, 136 patients with benign genitourinary disease (BD) and 50 healthy donors (HD). Urine Ln-γ2m was prospectively measured and accuracy was analyzed. Receiver operating characteristic (ROC) curves were determined and area under the ROC curve (AUC) was calculated for urine Ln-γ2m, and compared to those of traditional urine tumor markers such as nuclear matrix protein 22 (NMP22), bladder tumor antigen (BTA) and cytology. The net benefits of combining urine markers were analyzed by decision curve analysis. Mean urine Ln-γ2m was significantly higher in NMIBC than in BD or HD. The AUC for urine Ln-γ2m was significantly higher than those for urine NMP22, BTA or cytology when comparing NMIBC with HD. In patients with low-grade NMIBC, the AUC for urine Ln-γ2m was higher than the AUCs for NMP22, BTA or cytology. A net benefit of combined examination using urine Ln-γ2m/uCRN with NMP22 was demonstrated. These results suggest urine Ln-γ2m as a potentially useful biomarker for NMIBC, particularly in cases of low-grade cancer.

Comparison of urinary telomerase, CD44, and NMP22 assays for detection of bladder squamous cell carcinoma.

BackgroundSquamous cell carcinoma (SCC) of the bladder is common in many regions around the world. Prognosis is very poor, as most cases are diagnosed at an advanced stage due to a lack of affordable and valid screening markers for this type of cancer. The diagnostic accuracy of urinary nuclear matrix protein-22 (NMP22), telomerase activity, and CD44 were evaluated in urine samples of patients with bladder SCC.Materials and methodsWe conducted a case-control study comprised of 60 consecutive newly diagnosed bladder SCC patients diagnosed by cystoscopy and histopathological examination, and controls were 60 outpatients with benign urologic conditions and healthy clinic visitors. Urine samples collected from each subject underwent testing for NMP22, telomerase activity, and CD44. Descriptive and correlational statistical analysis of cases and controls were carried out and receiver operating characteristic curve analysis was used to determine optimal cut-off points for the three assays.ResultsArea under the curve was calculated at 0.96, 0.93, and 0.62 for NMP22, telomerase, and CD44, respectively. Urine levels of NMP22 and telomerase activity were significantly higher in the SCC group compared to controls (p < 0.001). Urine CD44 levels were not significantly higher in the SCC group compared to controls (p = 0.111). The overall sensitivity of NMP22, telomerase, and CD44 was 96.7%, 87%, and 45%, respectively, while the specificity was 85%, 88.6%, and 86.7%, respectively.ConclusionsUrinary telomerase activity, followed by NMP22 urine levels, showed high diagnostic yield and could hold potential promise as urinary biomarkers for the diagnosis of bladder SCC.

The Role of NMP22 and CSTB Levels in Predicting Postoperative Recurrence of Bladder Cancer

Objective To investigate the value of preoperative urinary nuclear matrix protein 22 (NMP22) and Cystatin B (CSTB) expressions in evaluating the postoperative recurrence of bladder cancer. Methods The clinical case data of 102 patients with bladder cancer who underwent surgical treatment from January 2017 to January 2022 were collected, and the patients were divided into a recurrence group (n = 54) and nonrecurrence group (n = 48) according to whether the patients recurred after surgery, and the preoperative NMP22 and CSTB expression levels between the two groups were compared. Receiver operating curve (ROC) was used to analyze the evaluation value of preoperative NMP22 and CSTB expression in patients with bladder cancer postoperative recurrence. Logistic multivariate regression method was used to analyze the correlation between preoperative NMP22 and CSTB expression and postoperative bladder cancer recurrence. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of NMP22 and CSTB single detection and combined detection were evaluated for postoperative recurrence of bladder cancer. Results The preoperative expression levels of NMP22 and CSTB in the recurrence group were significantly higher than those in the nonrecurrence group (P < 0.05). The results of ROC curve analysis showed that the AUC of preoperative NMP22 and CSTB expression levels to assess postoperative recurrence of bladder cancer was 0.696 and 0.659, respectively (P < 0.05). Logistic multivariate regression analysis showed that preoperative NMP22 and CSTB overexpression was an independent risk factor for postoperative recurrence of bladder cancer (OR = 1.042, 2.307, P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of preoperative NMP22 combined with CSTB in evaluating bladder cancer recurrence after surgery were higher than those of preoperative NMP22 and CSTB alone, and the differences were statistically significant (P < 0.05). Conclusion Preoperative NMP22 and CSTB conveying is hardly interrelated to postoperative recurrence of bladder carcinoma and has certain appraisal worth for postoperative recurrence of bladder carcinoma, and the combined testing of the two has a taller appraisal worth. NMP22 combined with CSTB detection will help to detect postoperative recurrence of bladder cancer and formulate effective treatment measures in time.

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.

Pioglitazone and the risk of bladder cancer: An Indian retrospective cohort study.

Aim:To determine whether pioglitazone is associated with an increased risk of bladder cancer among Indian type 2 diabetic patients.Methods:A retrospective data analysis of 2222 type 2 diabetic patients was conducted. The study subjects were divided into two equal groups: 1111 pioglitazone users and 1111 pioglitazone non-users. The safety of pioglitazone therapy was analyzed in terms of occurrence of bladder and other types of cancers along with its efficacy in terms of glycemic control. Parameters for assessing safety were duration of disease, duration of usage and total dose of pioglitazone consumed across age groups, glycemic control, obesity and family history of any cancer. Bladder cancer prevalence was analyzed on the basis of urinary cytology, urine routine and microscopy, hematuria, urinary nuclear matrix protein 22 analysis and ultrasonography.Results:Of the 2222 cases analysed, there was no evidence of bladder cancer in any of the studied groups, (p=not significant) which was also evident among 1111 patients on Pioglitazone therapy with a cumulative dose consumption of 2737 mg to 1,31,400 mg. On subgroup analysis, there was no evidence of bladder cancer amongst patients with age >60 years, duration of diabetes > 10 years and uncontrolled diabetics (HbA1c >8%) with cumulative pioglitazone consumption of >28,000 mg. A significant number of patients achieved good glycemic control (HbA1c <7.5%) with pioglitazone therapy.Conclusion:Pioglitazone therapy was not associated with occurrence of bladder cancer among Indian type 2 diabetic patients and demonstrated good glycemic control.

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.

239 - Immunodiagnostic Assay For Detecting Urinary Nuclear Matrix Protein 52 In Patients With Bladder Cancer

ABSTRACT Objective To report the rapid and simple detection of a nuclear matrix protein (NMP) in the urine of patients with bladder cancer using dot-enzyme-linked immunosorbent assay (ELISA). Patients and methods Urine sample from 120 patients with bladder cancer and 60 controls were evaluated using western blot and specific immunoglobulin G antibody to identify the urinary NMP marker using the developed dot-ELISA. The initial response and follow up of 82 patients treated by irradiation were followed using the assay. Results The NMP marker was identified in the urine of patients with cancer bladder at 52 KDa (NMP-52) by Western blot. The dot-ELISA detected the urinary NMP-52 marker in 85% of patients with squamous cell carcinoma and 92% with transitional cell carcinoma. The positive and negative predictive values (95% and 91% respectively) and efficiency (92%) of the dot-ELISA were high. NMP-52 tumor marker detection was correlated with the response to radiotherapy. Conclusion Detection of the urinary NMP-52 marker using dot-ELISA would be helpful in rapid diagnosis and follow up patients with bladder cancer. Disclosure All authors have declared no conflicts of interest.

Urinary Survivin mRNA Expression and Urinary Nuclear Matrix Protein 22 BladderChek® and Urine Cytology in the Detection of Transitional Cell Carcinoma of the Bladder

Objective: To compare the diagnostic performance of urine cytology (UC), survivin mRNA expression, and the NMP22 BladderChek® (NMP22BC) test for the detection, grading and staging of transitional cell carcinoma (TCC) of the bladder. Materials and Methods: 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. Results: 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 (χ² 8.5, p = 0.015). None of the three urine markers was significantly related to tumour pathological stages. Conclusion: The diagnostic sensitivity of urinary survivin mRNA expression was superior to that of UC and the NMP22BC test and correlates with tumour pathological grade but not stage.

Detection of Nuclear Matrix Protein 22 and Survivin Baseline Level in Patients after Radical Cystectomy

We investigated the baseline levels of urine nuclear matrix protein 22 (U-NMP22) and survivin in urine after radical cystectomy for primary invasive bladder cancer. We measured U-NMP22 and survivin values in 72 patients with four types of urinary diversion (Indiana bladder, Bricker bladder, Mainz bladder and orthotopic bladder) after radical cystectomy and 25 healthy volunteers. We also analyzed the relation between the U-NMP22 and survivin level and other variables among patients with continent urinary diversion and incontinent urinary diversion as well as healthy controls, and found that the U-NMP22 and survivin values were not associated with postoperative interval or gender. The U-NMP22 values (mean ± standard error) for continent urinary diversion, incontinent urinary diversion and healthy controls were 12.08 ± 0.10, 16.62 ± 0.15 and 0.01 ± 0.00 U/ml, respectively. The survivin values (mean ± standard error) for continent urinary diversion, incontinent urinary diversion and healthy controls were 0.47 ± 0.06, 0.69 ± 0.16 and 0.02 ± 0.03 U/ml, respectively. The U-NMP22 and survivin values in the Bricker bladder group were significantly higher than the values in the other three groups. We noted that increased levels of U-NMP22 and survivin after radical cystectomy varied according to different predictors, which may be useful for designing strategies to follow these cases.

Decision curve analysis assessing the clinical benefit of NMP22 in the detection of bladder cancer: secondary analysis of a prospective trial

• To employ decision curve analysis to determine the impact of nuclear matrix protein 22 (NMP22) on clinical decision making in the detection of bladder cancer using data from a prospective trial. • The study included 1303 patients at risk for 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, smoking and haematuria); 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. • In all, 72 patients were found to have bladder cancer (5.5%). In univariate analyses, NMP22 was the strongest predictor of bladder cancer presence (predictive accuracy 71.3%), followed by age (67.5%) and cytology (64.3%). • In multivariable prediction models, NMP22 improved the predictive accuracy of the base model by 8.2% (area under the curve 70.2-78.4%) and of the base model plus cytology by 4.2% (area under the curve 75.9-80.1%). • Decision curve analysis revealed that adding NMP22 to other models increased clinical benefit, particularly at higher threshold probabilities. • NMP22 is a strong, independent predictor of bladder cancer. • 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 avoid unnecessary cystoscopies, with minimal increased risk of missing a cancer.

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.

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.

The significance of urine NMP22 in the screening of urothelial cancer (comparison of ELISA and immunochromatography method)

e16024 Background: The early diagnosis of urothelial cancer allows for effective local treatment and optimizes the success of surgical therapy. Urine nuclear matrix protein 22 (NMP22) was introduced for the detection of transitional cell carcinoma. Add to old NMP22 (ELISA), new NMP22 (immunochromotography method : BladderChek) can be available from 2004. The objective of this study is to determine whether there are any correlation between urine NMP22 (two methods) and the grade or stage of urothelial cancer, and whether it can serve as a biochemical marker of urothelial cancer. Methods: A total of 246 patients with hematuria or followed up after TUR-BT, from March 2007 to December 2007,visited our hospital and subsequently underwent cystoscopy. The 246 patients provided voided urine samples. We immediately examined urine cytology and NMP22 (two methods). We set the cut off value on 12.0U/ml for NMP22 (ELISA). NMP22 (BladderChek) was judged by qualitative analysis. We decided that in urine cytology, classI,II,III were negative, while IV,V were positive by Papanicolaou classification. Results: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were 66.7 %, 98.3 %, 81.8 %, 96.3 % in urine cytology, 40.7 %, 75.9 %, 16.2 %, 91.8 % in NMP22 (ELISA), 59.3 %, 79.3 %, 24.6 %, 94.5 % in NMP22 (BladderChek). In 9 cases with false negative of urine cytology, 4 cases were picked up by NMP22 (ELISA), and 5 cases by NMP22 (BladderChek). Sensitivity of grade 1 was 33.3 % in urine cytology, while 66.7 % in NMP22 (BladderChek). By adding NMP22 (BladderChek) to urine cytology, sensitivity rose about 18 %. Conclusions: The sensitivity of urine cytology was unexpectedly high. NMP22 (BladderChek) is more useful than NMP22 (ELISA) because of higher sensitivity, specificity and advantage of simplicity, rapidity. It seems that the addition of NMP22 (BladderChek) to urine cytology is beneficial. No significant financial relationships to disclose.

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.

Could nuclear matrix protein 22 (NMP22) play a role with urine cytology in screening for bladder cancer? – experience at Kuwait University

This prospective study was undertaken to evaluate nuclear matrix protein (NMP22) compared to urine cytology in the detection of bladder cancer and also to determine whether indexing suspicious cytology to NMP22 could enhance the clinical utility of cytology. Cytological findings of voided urine collected prior to a cystoscopic biopsy were correlated with urine NMP22 assay in 46 patients attending the urology clinic in Mubarak Al-Kabeer Hospital. The patients were clinically categorized into newly diagnosed cases of transitional cell carcinoma (TCC), recurrent TCC, TCC in remission and controls. Using histological diagnosis as the gold standard the sensitivity and specificity of NMP22 were 78% and 43% respectively and of cases with malignant urine cytology were 30% and 87% respectively. If suspicious and malignant cytology were combined as positive results the sensitivity increased significantly to 87% while the specificity decreased but not significantly to 74%. Suspicious or malignant cytology enhanced by positive NMP22 gave a sensitivity of 70% and specificity of 87% neither of which was significantly different from cytology alone. There were three false positive cases on cytology and 13 false positive cases on NMP22 assay. There were three false negative cytology and five false negative NMP22 cases but only one was false negative for both, resulting in a high sensitivity (96%) but low specificity (30%) if either positive NMP22 or malignant or suspicious cytology was taken as a positive result. Combining NMP22 with malignant or suspicious cytological result improved sensitivity for the detection of bladder cancer but with a major decrease in specificity, suggesting a potential role in screening rather than diagnosis.