尿核基质蛋白22检测在膀胱癌诊断中的应用

目的　探讨尿核基质蛋白 2 2 (NMP2 2 )在膀胱癌诊断中的临床价值。方法　用化学发光分析法检测 2 7例膀胱癌和 2 2例疑似膀胱癌患者的NMP2 2 ,并同时行尿脱落细胞学检查。结果　膀胱癌和疑似膀胱癌患者尿NMP2 2 含量的中位数分别为 6 4 .10、12 .95U·mL-1,差异有显著性意义 (P <0 .0 1) ;尿NMP2 2 诊断膀胱癌敏感性为 85 .2 % ,特异性为 36 .4 % ;尿脱落细胞学诊断膀胱癌的敏感性为 18.5 % ,特异性为 10 0 %。结论　尿NMP2 2 检测可作为膀胱癌的辅助诊断手段     

Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China

Aim： To compare the results of bladder tumor associated antigen （BTA TRAK）, nuclear matrix protein 22 （NMP 22） and voided urine cytology （VUC） in detecting bladder cancer. Methods： A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups： （i） 93 patients with bladder cancer; （ii） 42 patients with urinary benign conditions; and （iii） 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results： The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion： The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.     

Comparative evaluation of the nuclear matrix protein,fibronectin, urinary bladder cancer antigen and voided urine cytology in the detection of bladder tumors

PURPOSE: We evaluate the diagnostic efficacy of nuclear matrix protein-22 (NMP22, Matritech, Newton, Massachusetts), fibronectin and urinary bladder cancer antigen (UBC, IDL Biotech, Borlange, Sweden) compared with voided urine cytology in the detection of bladder cancer. MATERIALS AND METHODS: A total of 168 patients provided a single voided urine sample for NMP22, fibronectin an ideal monoclonal for urinary bladder cancer and cytology before cystoscopy. Cystoscopy was done for all patients as the reference standard for identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. Of the 168 cases 100 were histologically diagnosed as bladder cancer, whereas the remaining 68 had benign urological disorders. A group of 47 healthy volunteers were also enrolled in this study. Voided urine was evaluated by NMP22, fibronectin and UBC, and their values were expressed relative to mg. creatinine. RESULTS: The optimal threshold values for NMP22, fibronectin and UBC were calculated by receiver operator characteristics curves as 27 units per mg. creatinine, 198 mg./mg. creatinine and 13 ng./mg. creatinine, respectively. The levels and positive rates of the 3 parameters were significantly higher in the malignant group compared to either the benign group or normal controls. Of the entire group NMP22, fibronectin and UBC were positive in 93.2%, 91% and 68.2%, respectively in bladder cancer cases with positive cytology. Moreover, these positive rates were significantly higher in bilharzial bladder cancer cases (58.8%, 67.5%, 58.8%, respectively) compared to nonbilharzial cases (35.6%, 36.3%, 31.1%). Overall sensitivity and specificity were 85% and 91.3% for NMP22, 83% and 82.6% for fibronectin, 67% and 80.8% for UBC and 44% and 100% for voided urine cytology. Combined sensitivity of voided urine cytology with the 3 biomarkers together was higher than either combined sensitivity of voided urine cytology with 1 of the biomarkers or than that of the biomarker alone. CONCLUSIONS: Our data indicate that NMP22 and fibronectin had superior sensitivities compared to UBC and voided urine cytology, while NMP22 and voided urine cytology had the highest specificities. The combined use of markers increased the sensitivity of cytology from 44% to 95.3%. The higher sensitivities of markers in bilharzial than nonbilharzial bladder cancer highlight their clinical use in screening patients with urinary bilharziasis.     

Impact of risk factors on the performance of the nuclear matrix protein 22 point-of-care test for bladder cancer detection

OBJECTIVES

To evaluate the impact of different risk factors and symptoms on the performance characteristics of the nuclear matrix protein 22 (NMP22) BladderChek® test (Matritech Inc., Newton, MA, USA) for the detection of bladder cancer, as this is a point‐of‐care assay that measures NMPs in voided urine.

PATIENTS AND METHODS

In all, 23 academic, private practice and veterans’ facilities in 10 states prospectively enrolled consecutive patients from September 2001 to May 2002. Participants included 1328 patients at elevated risk of bladder cancer from factors such as a history of smoking or symptoms including haematuria and/or dysuria. Patients at risk of malignancy of the urinary tract provided a voided urine sample for analysis of NMP22 protein and cytology before cystoscopy.

RESULTS

Of the 1328 patients: no urinary disease, benign disease and malignancy were found in 545 (41%), 704 (53%) and 79 (6%) patients, respectively. Overall, the positive predictive value (PPV) for detection of bladder cancer was 20.3% (45/222) and negative predictive value (NPV) was 96.9% (1072/1106). The PPV was higher in men (24.0%) than women (13.2%). In men, the PPV increased with smoking (35.4%), gross haematuria (51.2%) and a combination of both factors (70.6%). The impact on the PPV of smoking (9.7%) and gross haematuria (28.6%) was less dramatic in women. The PPV increased from 16.8% in patients aged <65 years to 23.5% in those aged >65 years. The NPV remained almost always >95% except in men with gross haematuria where it decreased to 77% in smokers and 94% in non‐smokers.

CONCLUSION

The PPV of the BladderChek test improves in patients at higher risk of bladder cancer reaching 77% in men presenting with gross haematuria who are aged >65 years and smoke. The NPV is highest in women aged <65 years, up to 100%.     

膀胱癌NMP22检测的临床病例对照研究

目的　探讨核基质蛋白 2 2 (NMP2 2 )在膀胱癌诊断和术后监测的作用。方法　采用临床流行病学病例对照研究方法 ,检测4 0例膀胱癌尿液中NMP2 2含量。结果　以美国FDA的诊断参考值 10U/mL为标准 ,本次研究的敏感性为 10 0 % ,特异性为 6 5 %。病例组NMP2 2明显高于对照组 ,病例组各个年龄段的NMP2 2无显著性差异 (P >0 .0 5 )。在病例组 ,随着膀胱癌病理分级和临床分期的增加 ,NMP2 2含量亦随之增加 (均P <0 .0 0 1) ,膀胱癌复发者NMP2 2明显高于未复发者 (P <0 .0 0 1)。结论　NMP2 2检测技术具有敏感性高、无创伤、可定量分析等优点 ,可以作为诊断膀胱癌和术后监测的一个指标     

联合核基质蛋白22 与膀胱肿瘤抗原监测膀胱肿瘤复发的意义

目的：探寻无创、快速、便捷的监测膀胱肿瘤复发的方法。方法：对90例TURBt术后患者，采用标准ELISA法检测尿核基质蛋白22（NMP-22）值，同时采用单抗免疫分析法测定膀胱肿瘤抗原（BTAstat）、膀胱镜检及病理检测有无肿瘤复发。结果：与膀胱镜检及活检结果相比，尿NMP-22检测可发现77％（33/43）复发病例，尿BTAstat检测可发现67％（29/43）复发病例。2项检测综合分析，检测准确率升至93％（40/43）。结论：尿NMP-22检测为快速、高效、便捷的监测膀胱肿瘤复发的方法，联合BTAStat检测可提高准确率，减少膀胱镜检频率。     

尿核基质蛋白22在膀胱癌术后复发监测中的应用

目的:探讨尿核基质蛋白22(NMP22)检测在膀胱癌术后复发监测中的应用价值.方法:采用ELISA法检测93例膀胱癌术后患者尿NMP22值,并分为复发组和未复发组进行比较.结果:复发组患者尿NMP22值高于未复发组(P＜ 0.01),以6 IU/L为最适临界值,敏感性 95.1%,特异性 69.2%,阳性预测值 70.9%,阴性预测值 94.7%.结论:尿NMP22检测可作为膀胱癌术后复发的常规监测方法,以6 IU/L为临界值是较适宜的.     

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 10U/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 NMP22was 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. This revised version was published online in September 2006 with corrections to the Cover Date.     

核基质蛋白22检测在膀胱癌筛查中的应用

目的：探讨检测核基质蛋白22(NMP22)在膀胱癌筛查中的应用价值。方法：检测129例血尿患者的尿NMP22，并分为膀胱癌组和非肿瘤组进行比较。结果：膀胱癌组患者尿NMP22值高于非肿瘤组(P＜0．01)。结论：尿NMP22检测具有较高的敏感性和特异性，在膀胱癌筛查中可以选择应用。     

Urinary level of nuclear matrix protein 22 in the diagnosis of bladder cancer: experience with 130 patients with biopsy confirmed tumor

PURPOSE: We prospectively evaluated the value of nuclear matrix protein 22 (NMP22dagger) and cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: We analyzed NMP22 in voided urine from 235 patients before cystoscopy. Of the patients 130 had transitional cell carcinoma of the bladder and subsequently underwent surgery. In a subset of 200 patients bladder washout samples for cytology were collected during cystoscopy. The cutoff for NMP22 was 10.0 units per ml. For cytology only high grade atypia was considered positive. RESULTS: Histology showed 77 superficial (pTa, pTis) and 53 invasive (pT1 or greater) tumors. Sensitivity of NMP22 was 51% and specificity was 83%. NMP22 sensitivity was 36% for superficial tumors and 73% for invasive transitional cell carcinoma. Overall sensitivity of cytology was 52% and specificity was 89%. Cytology sensitivity was 38% for superficial tumors and 83% for invasive transitional cell carcinoma. NMP22 sensitivity for grades 1, 2 and 3 tumors was 30%, 56% and 68%, respectively. Cytology sensitivity for grades 1, 2 and 3 tumors was 30%, 50% and 91%, respectively. Combined NMP22 and cytology had a sensitivity of 70%. CONCLUSIONS: NMP22 has sensitivity and specificity similar to those of cytology from bladder washout samples. Particularly in low stage and low grade tumors both tests show the same disappointing sensitivity. Because of a false-negative rate of 49%, NMP22 cannot replace cystoscopy in clinical practice, as the danger of missing NMP22 negative tumors is too high to rely on its results in an individual patient.     

膀胱癌患者尿NMP22与尿脱落细胞学检测的临床价值

目的研究核基质蛋白22（NMP22）与尿脱落细胞学在膀胱癌早期诊断、监测复发及判断预后中的临床价值。方法收集96份尿液标本,其中包括45例膀胱癌术前患者（经术后病理证实）,20例膀胱癌术后复测患者及3l例良性泌尿系疾病患者。均通过酶联免疫吸附法（ELISA）检测NMP22值,将其结果与尿脱落细胞学通过,检验的形式进行对比。结果45例膀胱癌术前患者NMP22的含量为9．3—112．5U／mL,中位数为48．7U／mL;31例良性泌尿系患者NMP22的含量为2．1～14．7U／mL,中位数为7．9U／mL;20例膀胱癌术后患者NMP22的含量为4．3～18．7U／mL,中位数为8．9U／mL,膀胱癌术前患者NMP22中位数明显高于良性泌尿系患者NMP22中位数,差异有显著统计学意义（P〈0．05）。以NMP22≥10U／mL为临界值,NMP22诊断膀胱癌的敏感性为82．2％,特异性为70．9％;尿细胞学的敏感性为31．1％。特异性为100％。20例膀胱癌术后患者经膀胱镜证实复发有9例。结论NMP22可以作为膀胱癌的早期筛查和术后随访的有效标志物。     

Neural network using combined urine nuclear matrix protein-22, monocyte chemoattractant protein-1 and urinary intercellular adhesion molecule-1 to detect bladder cancer

PURPOSE :We developed a neural network to identify patients with bladder cancer more effectively than hematuria and cytology. The algorithm is based on combined urine levels of nuclear matrix protein-22, monocyte chemoattractant protein-1 and urinary intercellular adhesion molecule-1. MATERIALS AND METHODS: A randomized double-blinded study of voided urine from 253 patients undergoing outpatient cystoscopy was performed. Of the patients 27 had bladder cancer on biopsy and 5 had muscle invasion. Urine tumor markers were measured using sandwich-enzyme-linked immunosorbent assay kits. Urine from patients with bladder cancer on cystoscopy was compared to urine from controls with negative cystoscopy results. An algorithm was created with 3 sets of cutoff values modeled to be 100% sensitive for superficial bladder cancer, 100% specific for superficial cancer and 100% specific for muscle invasive cancer, respectively. We compared our model to hematuria and cytology. RESULTS: For the hematuria dipstick test sensitivity, specificity, positive and negative predictive values were 92.6%, 51.8%, 18.7% and 98.2%, respectively. For atypical cytology sensitivity, specificity, positive and negative predictive values were 66.7%, 81%, 29.5% and 95.3%, respectively. For the sensitive model set sensitivity, specificity, positive and negative predictive values were 100%, 75.7%, 32.9% and 100%, respectively. For the specific model set sensitivity, specificity, positive and negative predictive values were 22.2%, 100%, 100% and 91.5%, respectively. For the muscle invasive model set sensitivity, specificity, positive and negative predictive values were 80%, 100%, 100% and 99.6%, respectively. The standard bladder tumor evaluation of 253 patients costs 61,054 US dollars but 36,450 US dollars using our model. CONCLUSIONS: Our algorithm is superior to conventional screening tests for bladder cancer. The model identifies patients who require cystoscopy, those with bladder cancer and those with muscle invasive disease. It provides possible savings over current screening methods. The potential loss of other information by not performing cystoscopy was not evaluated in our study.     

尿核基质蛋白22诊断尿路上皮癌的临床评价

目的 :评估尿核基质蛋白 2 2 (NMP2 2 )测定作为尿路上皮癌肿瘤标记物的临床应用价值。方法 :应用免疫酶标记法 (ELISA)检测 58例尿路上皮癌、32例良性泌尿系疾病、1 8例其他恶性肿瘤和 2 0例健康志愿者尿中 NMP2 2水平。尿路上皮癌组中有 2 9例患者在术后 5～ 7d再次检测其尿 NMP2 2。结果 :尿路上皮癌组的尿 NMP2 2平均为 2 9.4× 1 0 3u/L,明显高于良性泌尿系疾病组 (1 0 .1× 1 0 3u/L )、其他恶性肿瘤组 (8.6× 1 0 3u/L)和健康志愿者组 (5.7× 1 0 3u/L) (P <0 .0 0 1 ) ;尿路上皮癌患者尿 NMP2 2随肿瘤病理分级的递增而升高 ;复发病例 (46.9× 1 0 3u/L )高于初发病例 (2 1 .3× 1 0 3u/L ) (P <0 .0 1 ) ;2 9例尿路上皮癌患者术后复测尿 NMP2 2 ,结果较术前明显下降。结论 :尿 NMP2 2作为尿路上皮癌的肿瘤标记物具有较高的特异性 ,并可在一定程度上反应肿瘤的恶性程度和预后。     

A side by side comparison of cytology and biomarkers for bladder cancer detection

PURPOSE: The identification of accurate bladder tumor markers/tests could improve diagnosis, recurrence monitoring and treatment in patients with bladder cancer. In this study we compared the efficacy of the hyaluronic acid (HA)-hyaluronidase (HAase), BTA-Stat (Bard/Bion Diagnostics, Redmond, Washington), Hemastix (Bayer Corp., Elkhart, Indiana) (hematuria detection) and UBC-Rapid (IDL Biotech, Borl?nger, Sweden) tests, and cytology to detect bladder cancer. The HA-HAase test measures urinary HA and HAase levels, BTA-Stat detects complement factor-H and H related protein in urine, the Hemastix hemoglobin dipstick detects hematuria and UBC-Rapid detects cytokeratin 8 and 18 fragments in urine. MATERIALS AND METHODS: A total of 138 urine specimens from 115 patients were collected at University Hospital Hamburg-Eppendorf, including 59 with active bladder cancer and 79 with a history of bladder cancer (73) or with benign genitourinary conditions (6). Specimens were assayed by the HA-HAase test, BTA-Stat, Hemastix (hemoglobin dipstick) and UBC-Rapid. Cystoscopy and histological findings were used to make the clinical diagnosis. Cytology results were available on 92 patients. RESULTS: In a side by side comparison the HA-HAase test, cytology, BTA-Stat, Hemastix and UBC-Rapid had 88.1%, 70.6%, 52.5%, 50.8% and 35.6% sensitivity, and 81%, 81%, 76.7%, 78.2% and 75% specificity, respectively. The accuracy, and negative and positive predictive values of the HA-HAase test were the highest (84.1%, 90.1% and 77.6%), followed by cytology (77.2%, 82.5% and 68.6%), Hemastix (66.4%, 67.8% and 63.8%), BTA-Stat (66.2%, 67.8% and 63.3%) and UBC-Rapid (57.8%, 60% and 52.5%), respectively. CONCLUSIONS:: The HA-HAase test is superior to cytology, BTA-Stat, Hemastix and UBC-Rapid for detecting bladder cancer recurrence. A side-by-side comparison of tumor markers should help identify a marker for monitoring bladder cancer recurrence.     

Nomograms including nuclear matrix protein 22 for prediction of disease recurrence and progression in patients with Ta, T1 or CIS transitional cell carcinoma of the bladder

PURPOSE: We developed and validated nomograms that accurately predict disease recurrence and progression in patients with Ta, T1, or CIS transitional cell carcinoma (TCC) of the bladder using a large international cohort. METHODS: Univariate and multivariate logistic regression models targeted histologically confirmed disease recurrence, and focused on 2,542 patients with bladder TCC from 10 participating centers. Variables consisted of pre-cystoscopy voided urine Nuclear Matrix Protein 22 (NMP22) assay, urine cytology, age and gender. Resulting nomograms were internally validated with bootstrapping. Nomogram performance was explored graphically with Loess smoothing plots. RESULTS: Overall 957 patients had recurrent TCC. Tumor grade and stage was available for 898 patients, including 24% grade I, 43% grade II, and 33% grade III; 45% stage Ta, 32% T1 and/or CIS, and 23% T2 or greater. Bootstrap corrected predictive accuracy for any TCC recurrence was 0.842; grade III Ta/T1 or CIS was 0.869; and T2 or higher stage TCC of any grade was 0.858. Virtually perfect performance characteristics were observed for the nomograms predicting any TCC recurrence or grade III Ta/T1 or CIS. The nomogram predicting T2 or higher stage TCC overestimated the observed probability for predicted values greater than 45%. CONCLUSIONS: We developed and internally validated nomograms that incorporate urinary NMP22, cytology, age and gender to predict with high accuracy the probability of disease recurrence and progression in patients with Ta, T1, and/or CIS bladder TCC. These nomograms could provide a means for individualizing followup in patients with Ta, T1, CIS bladder TCC.     

Use of urinary biomarkers for bladder cancer surveillance: patient perspectives

PURPOSE: Interest has emerged in urinary biomarkers to replace or alternate with followup cystoscopies for routine bladder cancer surveillance. We assessed whether patients would accept a urine biomarker assay over flexible cystoscopy for monitoring bladder cancer. MATERIALS AND METHODS: We enrolled 200 consecutive patients previously diagnosed with superficial bladder tumors who were undergoing outpatient flexible cystoscopy as followup. Immediately after cystoscopy each patient completed a pain intensity numerical rating and was interviewed. The standard gamble method was applied to determine the minimal accepted diagnostic accuracy at which a urine test would be favored over cystoscopy for bladder surveillance. Clinical and demographic data with potential to affect patient preferences were analyzed. RESULTS: Of the 200 patients 75% would accept the results of a urine test as a replacement for cystoscopy only if it was capable of detecting more than 95% of recurrent bladder tumors and an additional 21% would accept it if the urine test was at least 90% to 95% accurate. Anxiety associated with the possibility of missing cancer was the major determinant of the minimal accepted accuracy. While male gender and higher pain intensity at cystoscopy were associated with willingness to accept a small level of uncertainty on univariate and multivariate analyses, the risk of progression to muscle invasion and the convenience of followup did not appear to affect patient preferences. CONCLUSIONS: From the patient perspective a urinary biomarker would likely require 95% or greater diagnostic accuracy to supplant cystoscopies for routine bladder surveillance. Inadequate sensitivity may be the major impediment to general acceptance of urinary biomarkers in this setting.     

Human complement factor H related protein test for monitoring bladder cancer

PURPOSE: The BTA stat test is a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine. We compared BTA stat test to voided urine cytology in patients monitored for bladder cancer in a prospective trial, and determined whether this test is effective in detection of recurrence not seen by regular cystoscopy. MATERIALS AND METHODS: A total of 445 consecutive patients with bladder cancer were studied. A voided urine sample was obtained before cystoscopy and divided for culture, cytology and BTA stat testing. In cases of a positive BTA stat test but negative cystoscopy, excretory urography or renal ultrasound, random biopsies and collected ureteral urine samples for ureteral cytology were obtained. The overall sensitivity and specificity as well as positive and negative predictive values for BTA stat test, cytology and their combination were calculated. RESULTS: Of the 445 patients 118 (26.5%) had bladder cancer recurrence on cystoscopy, which was detected by BTA stat test and cytology in 63 (53.4%) and 21 (17.8%), respectively. Of the remaining 327 patients not having recurrent tumor on cystoscopy 81 (24.8%) had a positive BTA stat test. Excretory urography or renal ultrasound and random biopsies in 48 (59.3%) of these patients revealed 7 recurrences, making the total number of recurrent tumors 125 of 412 (30.3%). The overall sensitivities and specificities for the BTA stat test, cytology and their combination were 56.0%, 19.2%, 60.0% and 85.7%, 98.3% and 85.0%, respectively. CONCLUSIONS: The sensitivity for detection of recurrent tumor on BTA stat test is superior to that of voided urine cytology in all bladder cancer categories, whereas the specificity of voided urine cytology is higher than that for BTA stat test. However, a sixth of the patients with apparent false-positive BTA stat test results chosen for further investigation had recurrent tumors that were not found on routine cystoscopy. Although the sensitivity and specificity were highest when both tests were used, the differences were not significant overall. Therefore, the BTA stat test could potentially replace urine cytology for followup of superficial bladder cancer.     

Urinary nuclear matrix protein 22 as a new marker for the screening of urothelial cancer in patients with microscopic hematuria

PURPOSE: The aim of the present study was to determine the clinical usefulness of nuclear matrix protein 22 (NMP22) as a new urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. METHODS: Patients with microscopic hematuria detected at a health examination, who were advised by a consulted urologist to have a cystoscopical examination, were asked to enter this study. Urine samples were collected before cystoscopy and divided into two portions for NMP22 test and voided urine cytology. RESULTS: Of the 309 patients with microscopic hematuria, 22 cases (7.1%) of urothelial cancer and one case of prostate cancer were detected. For the other cases, 128 (41.4%) were of benign diseases and 158 (51.1%) were designated as having no evidence of disease (NED). The median NMP22 values for urothelial cancer, other diseases and NED were 35.5, 6.7 and 6.0 U/mL, respectively, with 95% confidence intervals of 19.9-228.2, 5.1-9.3 and 5.4-7.2, respectively. The sensitivity of the NMP22 test for urothelial cancer was 90.9% (20/22), whereas the sensitivity of voided urine cytology was only 54.5% (12/22). CONCLUSIONS: The present study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.     

核基质蛋白22检测与尿脱落细胞学检查在膀胱癌诊断中的价值

目的　探讨尿核基质蛋白 2 2 (NMP 2 2 )检测和尿脱落细胞学检查在膀胱移行细胞癌诊断中的价值。　方法　对 15 5例怀疑膀胱癌者进行尿NMP 2 2与尿细胞学检查 ,其中 95例经组织学证实为膀胱移行细胞癌。比较两者诊断膀胱癌的敏感性和特异性。　结果　尿NMP 2 2的敏感性为6 5 .3%、特异性为 70 .0 % ;尿细胞学的敏感性为 4 3.2 %、特异性为 83.3%。NMP 2 2在膀胱癌不同分级和分期中的敏感性优于尿细胞学 (P <0 .0 5 )。　结论　尿NMP 2 2检测在早期诊断膀胱癌方面优于尿细胞学检查 ,可以作为膀胱癌的早期检测指标。     

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

OBJECTIVE

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).

PATIENTS AND METHODS

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.

RESULTS

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 (≥10 units/mL) and 80 (3.0%) had non‐TCC recurrence. Most of these, i.e. 60 (75%), were stage ≥T2. The sensitivity and specificity of urinary cytology were, respectively, 20.0% and 94.8%, vs 77.5% and 81.8% for NMP22 of ≥10 units/mL. The predictive accuracy of urinary cytology was 57.5%, vs 87.1% for NMP22 ≥ 10 units/mL. A combined model that included dichotomized NMP22 and urinary cytology was 85.3% accurate.

CONCLUSION

The ability of a NMP22 level of ≥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.