AIMTo 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.

METHODSA 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.

RESULTSThe 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.

CONCLUSIONThe 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.

Aged ; Humans ; Male ; Nuclear Proteins ; urine ; Taiwan ; Urinary Bladder Neoplasms ; diagnosis ; urine ; Urine ; cytology

OBJECTIVETo investigate the significance of telomerase activity in urine in the diagnosis and recurrence surveillance of urothelial carcinoma.

METHODSTelomerase activity in urine of 54 cases of urothelial carcinoma (urothelial carcinoma group) was estimated by polymerase chain reaction-enzyme-linked immunosorbent assay, and monitored continuously in 23 cases after tumor removal. 46 patients with benign urological diseases were also included as the control group.

RESULTSThe telomerase activity in urine of patients with urothelial carcinoma increased significantly as compared with the control group (P < 0.001), decreased into the normal range after tumor removal, and rose again upon intravesical tumor recurrence before the screening of recurrent tumors by cystoscopy. The higher the grade of tumor, the higher the telomerase activity; no correlation could be found between the preoperative level of telomerase activity in urine and recurrence.

CONCLUSIONSThe examination of telomerase activity in urine is helpful in the diagnosis of urothelial carcinoma and may be related to the differentiation degree of tumors. Its sensitivity is higher than that of cystoscopic examination and may become an important ancillary method in the screening of urothelial carcinoma recurrence.

Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; diagnosis ; urine ; Sensitivity and Specificity ; Telomerase ; urine ; Urinary Bladder Neoplasms ; diagnosis ; urine

OBJECTIVETo evaluate the urinary nuclear matrix protein (NMP22) as an adjuvant diagnostic index for transitional cell carcinoma of urinary tract and monitoring the state of disease.

METHODSUrinary samples were collected from 262 patients with transitional cell carcinoma, 198 non-transitional cell carcinoma of the urinary tract and 65 patients with benign diseases. Urinary NMP22 concentration was determined through enzyme linked immunosorbent assay (ELISA).

RESULTSThe urinary NMP22 concentration had significant difference among the three groups (Kruskal Wallis, chi(2) = 197.17 P < 0.001). The detection sensitivity and specificity of urinary NMP22 to transitional cell carcinoma were 71.37% and 87.69% respectively. The NMP22 concentration showed significant difference among three groups divided according to the pathological grade (Kruskal-Wallis test, chi(2) = 34.06 P < 0.01). The NMP22 concentration was significant lower in the recovery patients after the operation than the peoples of pre-operation and recurrence (Kruskal-Wallis test, chi(2) = 37.53, P < 0.001).

CONCLUSIONMP22 is a helpful tumor marker for the diagnosis of transitional cell carcinoma and monitoring the state of illness with increased efficacy.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; urine ; Carcinoma, Transitional Cell ; diagnosis ; urine ; Child ; Female ; Humans ; Male ; Middle Aged ; Nuclear Proteins ; urine ; Urinary Bladder Neoplasms ; diagnosis ; urine

OBJECTIVETo investigate the significance of apolipoprotein (Apo)-A1 in urine as a biomarker for early diagnosis and classification of bladder urothelial carcinoma (BUC).

METHODSUrine samples were divided into four groups: normal control group, benign bladder disease group, low-grade malignant BUC group, and high-grade malignant BUC group. Apo-A1, which showed significantly different expression among the four groups, was selected according to the two-dimensional electrophoresis (2-DE) images of the four groups, and enzyme-linked immunosorbent assay (ELISA) was used to quantify Apo-A1 in the four groups. A receiver operating characteristic (ROC) curve was generated, and the optimal operating points on the ROC curve were found to determine the critical concentrations of Apo-A1 for early diagnosis of BUC and differentiation of low-grade and high-grade malignant BUC. The results were verified clinically, and the specificity and sensitivity were calculated.

RESULTSThe 2-DE images showed that that the level of Apo-A1 increased from the normal control grouP to high-grade malignant BUC group. The ELISA showed that there was no significant difference in Apo-A1 level between the normal control grouP and benign bladder disease group, but the Apo-A1 level was significantly higher in the BUC groups than in the normal control grouP and benign bladder disease grouP (P < 0.01); the high-grade BUC grouP had a significantly higher Apo-A1 level than the low-grade BUC grouP (P < 0.01). The BUC patients and those without BUC could be differentiated with an Apo-A1 concentration of 18.22 ng/ml, while the low-grade and high-grade malignant BUC could be differentiated with an Apo-A1 concentration of 29.86 ng/ml. When used as a biomarker, Apo-A1 had a sensitivity of 91.6% (98/107) and a specificity of 85.7% (42/49) for diagnosis of BUC and had a sensitivity of 83.7% (41/49) and a specificity of 89.7% (52/58) for BUC classification.

CONCLUSIONApo-A1 may be a biomarker for early diagnosis and classification of BUC and shows promise for clinical application.

Aged ; Apolipoprotein A-I ; urine ; Early Detection of Cancer ; Female ; Humans ; Male ; Middle Aged ; Urinary Bladder Neoplasms ; diagnosis ; urine

BACKGROUND: Screening of high-risk patients using bladder tumor markers can offer an advantage of early detection and saving medical costs. For these purpose many tumor markers have been developed to supplement invasive cystoscopy. Our study evaluated the NMP22 point-of-care test (NMP22 POCT), which is one of the tumor makers, comparing with the standard urine cytology for the diagnosis of bladder cancer. METHODS: From January to September 2005, 232 patients who had undergone a cystoscopy due to bladder cancer associated symptoms including hematuria and dysuria were enrolled in this study. Urine specimens were collected for NMP22 POCT and cytology. NMP22 POCT and urine cytology were compared for sensitivity and specificity. In addition, we evaluated urine stick test and microscopy to explain some false-positive results in NMP22 POCT. RESULTS: Superficial transitional cell carcinoma was diagnosed in 10 patients. The sensitivity of NMP22 test was 60% (95% confidence interval [CI], 26.2-87.8%), whereas that of cytology was 33.3% (95% CI, 7.5-70.1%); however, the difference was not significant. The specificity of NMP22 test was 69.8% (95% CI, 63.3-75.8%), compared with 99.0% (95% CI, 96.5-99.9%) for cytology (P<0.001). The presence of microscopic RBCs in urine specimen was significantly associated with the lower specificity of NMP22 POCT (P=0.02). CONCLUSIONS: NMP22 POCT was significantly less specific than urine cytology. To be useful as a bladder cancer screening test, the NMP22 test should have a higher specificity.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Nuclear Proteins/*urine ; Point-of-Care Systems ; Sensitivity and Specificity ; Tumor Markers, Biological/*urine ; Urinary Bladder/pathology ; Urinary Bladder Neoplasms/*diagnosis/urine ; Urine/cytology

BACKGROUND AND OBJECTIVESurvivin has gradually become an important target in diagnosis, prognosis prediction and treatment of tumor. There are many studies on urine-based survivin mRNA test using reverse transcription-polymerase chain reaction (RT-PCR) as a noninvasive examination for bladder cancer. However, its clinical value remains controversial. This study was to evaluate the diagnostic value of urine survivin mRNA detection with RT-PCR for bladder cancer by a systematic review of related studies.

METHODSWith the search terms such as bladder neoplasm, survivin, RT-PCR, sensitivity, specificity and diagnosis, we systematically searched through PubMed, EMBASE, SCI, Cochrane Library, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Full-text Database (CSJD), China Journal Full-text Database (CJFD), Chinese Medical Association (CMA) digital periodicals and Google Scholar totally from January 1997 to April 2009 for diagnostic trials with RT-PCR detection of urine survivin mRNA for bladder cancer. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) items were used to evaluate the quality of the included studies. Meta-disc software was used to calculate outcome indicators.

RESULTSTwenty-six studies, totally 2 416 patients, were eligible. Meta-analysis showed that compared with pathologic examination, the summary values of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and summary receiver operating characteristic curve (SROC) of urine-based survivin mRNA test using RT-PCR for bladder cancer were 88%, 94%, 14.56, 0.13 and 0.9736, respectively. Nested RT-PCR got the highest sensitivity, specificity and SROC and the values were 91%, 95% and 0.9805, respectively. The sensitivity and specificity of general RT-PCR were the second highest, which were 87% and 94%, respectively. The sensitivity of quantitative RT-PCR was 80% and the specificity was 93%.

CONCLUSIONSComparing with pathologic examination, the sensitivity and specificity of urine-based survivin mRNA test using RT-PCR are relatively high. It can be used as an important adjunct method for cystoscope in early screening and postoperative monitoring of bladder cancer.

Databases, Bibliographic ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; urine ; RNA, Messenger ; urine ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Sensitivity and Specificity ; Urinary Bladder Neoplasms ; diagnosis ; genetics ; urine

OBJECTIVETo investigate a non-invasive, effective and rapid mode of detecting the recurrence of bladder cancer during follow-up.

METHODSNinety patients following transurethral resection of bladder tumor (TURBt) surgery were recruited from January 1998 to March 2000. Standard ELISA was used to determine the quantity of nuclear matrix protein (NMP-22) in urine of all bladder cancer patients during their follow-up periods. Urine bladder tumor antigen (BTA) stat test was simultaneously performed and followed by cystoscopy.

RESULTSThe total positive rates of urinary NMP-22 and BTA stat test were 76.7% (33/43) and 67.4% (29/43), respectively. Comparatively, this positive rate would increase to 93.0% (40/43) when the combination of both urine NMP-22 and BTA test were adopted.

CONCLUSIONExamination of NMP-22 in urine is a rapid and effective way to detect the recurrence of bladder cancer. If combined with BTA test, NMP-22 may be used as a non-invasive method in surveillance of recurring of bladder cancer, which may reduce the frequency of patients needing to undergo conventional invasive cystoscopy.

Antigens, Neoplasm ; analysis ; Humans ; Neoplasm Recurrence, Local ; diagnosis ; Neoplasm Staging ; Nuclear Proteins ; urine ; Sensitivity and Specificity ; Urinary Bladder Neoplasms ; diagnosis

OBJECTIVETo investigate the difference in urinary proteome between patients with bladder urothelial carcinoma (BUC) and healthy volunteers and to provide a basis for the early diagnosis of BUC.

METHODSThe urine samples from BUC patients and healthy volunteers (controls) were treated by 25% ethanol precipitation and two-dimensional gel electrophoresis (2-DE), and the obtained urinary proteins were subjected to Coomassie brilliant blue staining and analysis by PDQuest 8.0 (2-DE image analysis software); the differentially expressed proteins were sequenced by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry and identified using the Swiss-Prot database; the differential expression of these proteins was verified by western blot.

RESULTSHigh-resolution and high-reproducibility 2-DE images were obtained from the urine samples of BUC patients and controls, with 789 ± 18 and 762 ± 14 protein spots, respectively. Compared with the control group, the BUC grouP had significantly decreased expression of 6 protein spots and significantly increased expression of 11 protein spots. The mass spectrometry revealed five proteins with increased expression in the BUC group, including fibrinogen, lactate dehydrogenase B, apolipoprotein A1, clusterin, and haptoglobin, and the results were confirmed by western blot.

CONCLUSIONThere is significant difference in urinary proteome between BUC patients and healthy volunteers; the identification of differentially expressed proteins in urine lays the foundation for identifying potential molecular markers in early diagnosis of BUC.

Aged ; Case-Control Studies ; Early Detection of Cancer ; Female ; Humans ; Male ; Middle Aged ; Proteomics ; methods ; Urinary Bladder Neoplasms ; diagnosis ; urine

BACKGROUND: As bladder cancer is a superficial tumor with frequent recurrences, early detection and confirmation of recurrence are important. We evaluated the usefulness of NMP22 BladderChek (NMP22BC) for the diagnosis and monitoring of bladder cancer. METHODS: From July to December 2004, we enrolled in the study 670 patients who visited the urology clinic in Ewha Womans University, Dongdaemun Hospital with hematuria or dysuria and were tested with NMP22BC. We also performed the NMP22BC and BTA stat tests simultaneously in 21 patients and interference test in 10 patients. RESULTS: NMP22BC tests were negative in 97% of the patients who had been cured of bladder cancer and were positive in 95% of the patients with recurred bladder cancer. The diagnostic sensitivity, specificity, positive and negative predictive value, and efficiency were 95.0%, 91.5%, 25.7%, 99.8%, and 91.6%, respectively, with 8.5% false positive and 5% false negative rates. Fifty-five patients showed false positive in the NMP22BC test, the main cause of which was the presence of WBCs in urine. There was a good agreement between the NMP22BC and BTA stat tests (kappa agreement value, 0.5; P=0.008). According to the interference test, two patients with more than 3+ in leukocyte esterase results showed false positive in the NMP22BC test. CONCLUSIONS: NMP22BC test was simple to perform, rapid to produce the results, and useful in diagnosing a bladder cancer recurrence; the test shows a high efficiency with a high sensitivity, specificity, negative predictive value, and low false negative rate.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; Nuclear Matrix-Associated Proteins/*urine ; Nuclear Proteins/*urine ; Reagent Kits, Diagnostic ; Urinary Bladder Neoplasms/*diagnosis

OBJECTIVETo evaluate the expression and clinical significance of urinary nuclear matrix protein (NMP22) and cytokeratin 18 (CK18) for transitional cell carcinoma of the bladder.

METHODSUrinary 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).

RESULTSThe 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).

CONCLUSIONNMP22 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.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; urine ; Carcinoma, Renal Cell ; urine ; Carcinoma, Transitional Cell ; diagnosis ; pathology ; surgery ; urine ; Child ; Female ; Follow-Up Studies ; Humans ; Keratin-18 ; urine ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; urine ; Neoplasm Staging ; Nuclear Proteins ; urine ; Prognosis ; Sensitivity and Specificity ; Urinary Bladder Neoplasms ; diagnosis ; pathology ; surgery ; urine ; Young Adult