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     

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.     

Comparison of cytology and nuclear matrix protein 22 for the detection and follow-up of bladder cancer

OBJECTIVES: This study was designed to determine the clinical usefulness of the nuclear matrix METHODS: 84 patients suffering from bladder cancer or suspected bladder cancer, 25 patients with benign urological lesions and 60 healthy controls participated in a prospective study. Freshly voided spot urine samples were taken for cytological examination and determination of NMP 22 levels by enzyme-linked immunoassay. RESULTS: The sensitivity of the NMP 22 test according to the tumor grading was (results of cytology in brackets): G1 25.0% (20.0%); G2 68.2% (59.1%), and G3 100.0% (66.7); overall sensitivity was 62.5% (45.0%). The sensitivity for superficial bladder cancer was 46.7% (36.7%) and for invasive bladder cancer 90.0% (70.0%). The specificity was 65.9% (88.9%). CONCLUSIONS: NMP 22 is a reliable tool for detecting invasive bladder cancer. Results for the frequently occurring low grade superficial bladder cancer are as poor as those obtained with cytology. In addition benign lesions such as urolithiasis or urinary tract infection lead to false-positive results. Therefore cystoscopy has to be performed when trying to detect and follow-up bladder cancer.     

尿核基质蛋白22浓度与膀胱移行细胞癌病理分级分期关系的研究

目的探讨尿核基质蛋白22（NMP22）与膀胱移行细胞癌病理分级分期的关系。方法对1999年6月至2005年3月间就诊的642例膀胱癌患者行尿液NMP22检测,检测后1周-1个月内行膀胱镜和病理学检查,按病理分级分为3组,G1组为69例（男58例、女11例）,G2组为375例（男255例、女120例）,G3组为198例（男143例、女55例）,比较中位数NMP22浓度。同时,对其中239例患者按病理分期分为3组,PT1组为121例（男76例、女45例）,PT2组为65例（男37例、女28例）,PT3组为53例（男36例、女17例）,比较中位数NMP22浓度。结果G1、G2和G3组之间中位数NMP22浓度比较,差异有统计学意义（X^2=67．547,P〈0．001）;PT1、P12和PT3组之间中位数NMP22浓度比较,差异有统计学意义（X^2=20．629,P〈0．001）。结论尿NMP22浓度与膀胱移行细胞癌的病理分级、分期有相关关系。     

Clinical evaluation of urinary nuclear matrix protein 22 as a marker for bladder cancer]

The purpose of this study is to evaluate the clinical usefulness of urinary nuclear matrix protein 22 (NMP22) as a marker for bladder cancer. We examined the positive rates of NMP22 test, urinary cytology and bladder tumor antigen (BTA) test, and compared the positive rate of NMP22 test with that in urinary cytology and BTA test. Urine samples were obtained from 50 patients with histologically confirmed bladder cancer before the treatment. The samples were examined by NMP22 test, urinary cytology and BTA test. In 50 patients with bladder cancer, the overall positive rate was 40% for NMP22 test, 40% for urinary cytology, and 16% for BTA test. A combination of NMP22 test and urinary cytology showed a significantly higher positive rate (54%) as compared to NMP22 test or urinary cytology alone. When NMP22 test and urinary cytology were compared for tumor size, number, shape, stage and grade, NMP22 test showed a significant higher positive rate than urinary cytology in grade 1 bladder cancer. In conclusion, although NMP22 test and urinary cytology gave a similar positive rate, a combination of NMP22 test and urinary cytology is more useful than the NMP22 test or urinary cytology alone for monitoring of bladder cancer.     

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。     

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.     

Initial tumor stage and grade as a predictive factor for recurrence in patients with stage T1 grade 3 bladder cancer

PURPOSE: We evaluated whether the risk of progression and the recurrence rate were different in patients with primary and nonprimary stage T1 grade 3 transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Between 1983 and 1997, 75 patients were treated for stage T1 grade 3 transitional cell carcinoma of the bladder. Of these patients 68 (primary and nonprimary tumor in 58 and 14, respectively) without carcinoma in situ who had not undergone complete cystectomy immediately after diagnosis were included in the study. No maintenance regimen was used. Median followup was 100 months (range 9 to 217). RESULTS: The incidence of multiple tumors in patients with nonprimary tumors was significantly higher than in patients with primary disease (p = 0.035). However, the recurrence-free survival rate in patients with primary T1 GIII bladder tumor was significantly lower than that of patients with nonprimary T1 GIII bladder tumor (p = 0.0016). Multivariate analysis using Cox's proportional hazard regression model revealed that only initial tumor status had statistically significant effects on tumor recurrence (p = 0.007) and no other factors had a significant influence on recurrence-free survival. Progression-free and cancer specific survival rates were also significantly different between the 2 groups (p = 0.036 and 0.0307, respectively). CONCLUSIONS: Our study indicates that patients with primary stage T1 grade 3 bladder cancers have higher recurrence and progression potential than those with nonprimary disease despite the higher incidence of multiple tumors in patients with nonprimary tumors.     

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.     

Clinical evaluation of urinary NMP22 (nuclear matrix protein 22) bladder chek in the detection of patients with bladder cancer

The clinical usefulness of the nuclear matrix protein 22 (NMP22) Bladder Chek test as a novel urine marker in the detection of patients with bladder cancer was evaluated in comparison with the urinary NMP22 enzyme-linked immunosorbent assay (ELISA) and urinary cytology. A total of 40 patients with pathologically proven bladder cancer voided urine specimen before treatment. The urine samples were divided for NMP22 Bladder Chek test, NMP22 ELISA, and urinary cytology. In the 40 patients with bladder cancer, the overall positive rate was 62.5% for the NMP22 Bladder Chek test, 55% for the NMP22 ELISA test, and 27.5% for urine cytology. There was a significant difference between NMP22 Bladder Chek, NMP22 ELISA and cytology. The positive rate with the NMP22 Bladder Chek and NMP22 ELISA was higher in the patients with high grade and large-size (1 cm < or =) tumor. In 40 patients presenting with microhematuria without urothelial cancer, the false positive rate 12.5, 10, and 0% for NMP22 Bladder Chek, NMP22 ELISA, and urinary cytology. No significant difference was found with the test. In conclusion, the urine NMP22 Bladder Chek test provided a higher positive rate than the NMP22 ELISA test and urinary cytology. Therefore, the NMP22 Bladder Chek test may be clinically more useful as a tumor marker for the diagnosis of bladder cancer.     

膀胱癌患者尿NMP22测定的临床意义

目的：评价尿核基质蛋白22（NMP22）在膀胱癌诊断和预后判定中的应用价值。方法：采用ELISA法测定18例膀胱癌和20例泌尿系良性疾病患者尿液中NMP22值,及10例膀胱移行细胞癌患者术后尿NMP22值。结果：18例膀胱癌患者尿NMP22的中位值为44．3IU／L,20例泌尿系良性疾病患者尿NMP22的中位值为5．8IU／L,二者相比判别有显著性意义（P＜0．02）。以10IU／L为临界值,诊断膀胱癌的敏感性为83％,特异性为70％,阴性预测值为82％。10例膀胱移行细胞癌患者术后尿NMP22中位值为7．8IU／L,与术前相比明显下降（P＜0．01）。尿NMP22在肿瘤分级间的差别无显著性意义。结论：尿NMP22作为一种灵敏、简便的早期诊断膀胱癌的瘤标,对于预后判断可能具有应用价值。     

尿端粒酶、NMP22和ImmunoCyt联合检测在膀胱癌诊断中的应用

目的评价尿端粒酶、核基质蛋白22（NMP22）和ImmunoCyt测定在膀胱癌（BTCC）早期诊断中的应用价值,寻找早期诊断膀胱癌的有效方法。方法选择60例经病理诊断明确为早期膀胱移行细胞癌和60例非膀胱肿瘤患者,分别进行尿端粒酶、ImmunoCyt、NMP22和标准尿脱落细胞学检测。结果尿端粒酶、NMP22和ImmunoCyt和尿脱落细胞学的敏感度分别为58.3%、60.0%、61.6%、26.6%;准确度分别为75.8%,78.3%,78.3%和63.3%;特异度分别为93.3%,96.6%,95.0%和100%。三者联合检测与尿端粒酶、NMP22和ImmunoCyt单独检测相比,敏感度（分别为χ2=6.53,P〈0.05;χ2=5.17,P〈0.05;χ2=4.54,P〈0.05）和准确度（分别为χ2=4.01,P〈0.05,χ2=4.38,P〈0.05,χ2=4.91,P〈0.05）都有所提高;尿端粒酶、NMP22和ImmunoCyt联合检测的敏感度（χ2=28.06,P〈0.01）和准确度（χ2=16.2,P〈0.01）均高于尿脱落细胞学,差异有统计学意义。结论尿端粒酶、NMP22和ImmunoCyt是早期诊断膀胱移行细胞癌的一种高特异性指标,三者联合检测能提高膀胱癌的早期诊断率。     

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.     

Surveillance of stage O, grade I bladder cancer by cytology alone--is it acceptable?

Although the high incidence of subsequent tumors is well established there is accumulating evidence that few cases of low grade, low stage transitional cell carcinomas will progress in stage. Since the purpose of intensive endoscopic monitoring following initial tumor resection is to detect potentially lethal new tumors as soon as possible, we reviewed retrospectively the course of 36 patients with an initial grade I, stage O (Ta) transitional cell carcinoma to determine whether cytology was capable of achieving this goal. Of these patients 10 (28 per cent) had a subsequent tumor of a higher grade or stage. Cytology performed at or before recurrence was positive in 8 patients (80 per cent) and 2 (20 per cent) had grade II, noninvasive transitional cell carcinoma with negative cytology. Subsequent tumors in these 2 patients have been grade I. All 36 patients are alive. Given the patient inconvenience, expense and risk of infection of cystoscopy compared to cytology, this retrospective review suggests that when an experienced cytopathologist is available patients with grade I, noninvasive transitional cell carcinoma may be monitored primarily by urinary cytology with less frequent endoscopy. A prospective study must be performed to confirm this approach.     

A comparison of urinary nuclear matrix protein-22 and bladder tumour antigen tests with voided urinary cytology in detecting and following bladder cancer: the prognostic value of false-positive results

OBJECTIVES: To evaluate the diagnostic and prognostic value of the nuclear matrix protein-22 (NMP22) and bladder tumour antigen (BTAstat) tests compared with voided urinary cytology (VUC) in detecting and following bladder cancer, assessing particularly the prognostic value of false-positive test results in patients followed up for bladder cancer. PATIENTS AND METHODS: From 739 patients suspected of having bladder cancer, voided urine samples for the NMP22 and BTAstat tests, and for VUC and urine analysis, were collected before cystoscopy. All patients underwent transurethral resection of bladder lesions or mapping. and were followed for a mean (range) of 27.3 (3-65) months. RESULTS: In the 406 patients with bladder cancer, the overall sensitivity was 85% for NMP22, 70% for BTAstat and 62% for VUC. For histological grades 1-3 the sensitivity in detecting transitional cell carcinoma was 82%, 89% and 94% for NMP22, 53%, 76% and 90% for BTAstat, and 38%, 68% and 90% for VUC, respectively. Although the sensitivity in detecting invasive carcinoma was >85% for all the tests. NMP22 and BTAstat were statistically more sensitive than VUC for superficial tumours. The optimal threshold value for NMP22, calculated using the receiver operating characteristics curve was 8.25 U/mL. The specificity was 68% for NMP22, 67% for BTAstat, and 96% for VUC. The specificity of VUC remained >87% and was independent of benign histological findings. In contrast, in patients with no apparent genitourinary disease on histology, NMP22 and BTAstat had significantly higher specificity (94% and 92%, respectively: P=0.003) than in the group with chronic cystitis (52% for both tests). Forty patients having no bladder cancer at biopsy had a recurrence after a mean (range) follow-up of 7.7 (3-15) months: all had a previous history of bladder cancer. According to subsequent recurrence, the prognostic positive and negative predictive values were 18% and 91% for NMP22, 13% and 88% for BTAstat, and 79% and 91% for VUC. Both false-positive VUC and NMP22 tests predicted recurrence (log-rank test, P<0.001 and P=0.004, respectively), but the BTAstat test produced no similar correlation (P=0.778). CONCLUSION: The NMP22 and BTAstat tests are better than VUC for detecting superficial and low-grade bladder cancer but they have significantly lower specificity. After excluding diseases with the potential to interfere in these tests the overall specificity of both tests is increased considerably. False-positive results from NMP22 and VUC but not from BTAstat in patients followed up for bladder cancer correlate with future recurrences.     

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。