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[Availability of NMP22 (nuclear matrix protein 22) for the diagnosis of urothelial cancer].

We evaluated the availability of NMP22 for the diagnosis of urothelial cancer. Of 154 patients with gross hematuria or microscopic hematuria, 14 patients with bladder cancer and 4 patients with upper urothelial cancer were detected. Of 73 patients continued to be followed for urothelial cancers, 11 patients with bladder cancer were detected. NMP22 was not available when a large number of RBC was present in urine. Also, NMP22 was significantly higher in patients with urothelial cancers. Interpretation of the ROC curve indicated an optimal cutoff value of 9.2 u/ml. Using 9.2 u/ml as a cutoff, the sensitivity and specificity were, respectively 87.0% and 64.0% in patients with hematuria, and 81.8% and 78.7% in patients with a history of TCC. This indicated that when NMP22 was used for the diagnosis of urothelial cancers, 12.0 u/ml, the value recommended as a cutoff in Japan, might be too high to differentiate patients with urothelial cancers.

Biomarkers, Tumor↗

Comparison of nuclear matrix protein 22 and bladder tumor antigen in urine of patients with bladder cancer.

Recently, two new tumor markers for bladder cancer have been introduced: NMP22 test and BTA TRAK assay. This study was designed to evaluate the urinary values of these two proteins using quantitative enzyme immunoassays in well microplates. Urine samples from 47 healthy subjects, 26 with benign genitourinary disorders and 109 patients with a histological diagnosis of bladder cancer were collected. The specificity, the positive predictive value, the negative predictive value and the efficiency were established for NMP 22 and BTA, and the cut off values were fixed at a specificity of 95% in the benign disease group (12 U/ml and 23 U/ml respectively). We observed a very high concordance between the two urinary tumor markers (73%), although the overall sensitivity of BTA in bladder cancer patients seems to be better than that of NMP22 (62% vs 54% respectively), especially in the superficial disease group (36% for BTA and 14% for NMP22).

Adult↗

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

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

Adult↗

[Cytokeratins (UBC and CYFRA 21-1) and nuclear matrix proteins (NMP22) as urine tumor markers in the diagnosis of bladder cancer].

BACKGROUND: The development of urinary tumor markers such as UBC, CYFRA 21-1 and NMP22 appeared to be non invasive alternative methods for the detection of bladder cancer. We compared the individual and combined sensitivity of the urinary tumor markers in the detection of bladder cancer, contrasting them with the conventional diagnostic procedures. PATIENTS AND METHODS: 237 voided urines from subjects under risk for bladder cancer were collected immediately before the endoscopic examinations: 44 patients under suspicion of a primary bladder tumor and 193 patients under follow-up of a previous bladder cancer were included. UBC and NMP22 were measured by enzyme-immunoabsorbent-assays and CYFRA 21-1 by an electro-chemiluminescense-immunoassay. RESULTS: Taking the cutoffs of 9.7 micrograms/l for UBC, 5.4 ng/ml for CYFRA 21-1 and 10.0 U/ml for NMP22 sensitivities were 70%, 69% and 67% for UBC, CYFRA 21-1 and NMP22 at specificities of 95%, 94% y 80%, respectively. All tumor markers showed higher sensitivities than urinary cytology (7%), microhematuria (62%) and gross hematuria (10%) at specificities of 99%, 78% and 99%, respectively. The combinations of NMP22 plus CYFRA 21-1 reached the highest sensitivity (79%), slightly lower than simultaneously measuring the three tumor markers (80%). CONCLUSIONS: The sensitivities of the urinary markers UBC, CYFRA 21-1 and NMP22 appeared to be high enough so as to substitute urinary cytology. The diagnostic similarity between cytokeratins individually and in each type of patients might not recommend their simultaneous determination. The combined measurement of NMP22 and one cytokeratin marker (CYFRA 21-1 or UBC) appeared to be the most recommended.

Adult↗

Variability in the performance of nuclear matrix protein 22 for the detection of bladder cancer.

PURPOSE: We assessed variability in the diagnostic performance of NMP22 for detecting recurrence and progression in patients with Ta, T1, and/or CIS transitional cell carcinoma of the bladder in a large international cohort. MATERIALS AND METHODS: NMP22 voided urine levels were measured in 2,871 patients who underwent office cystoscopy for monitoring previous stage Ta, T1 and/or CIS transitional cell carcinoma at 12 participating institutions. RESULTS: Patient characteristics varied considerably among institutions. Overall 1,045 patients (36.4%) had recurrent transitional cell carcinoma (range across institutions 13.6% to 54.3%). Median NMP22 was 5.5 U/ml (range across institutions 2.5 to 18.8). Of the patients 33.5% had grade III tumors (range across institutions 20.6% to 54.0%) and 22.4% had muscle invasive tumors (range across institutions 3.2% to 38.2%). Area under the ROC curve for bladder TCC detection was 0.735 (95% CI 0.715 to 0.755, range across institutions 0.676 to 0.889). The manufacturer recommended cutoff of 10 U/ml detected 57% of cases with a 19% false-positive rate. AUC for grade III and stage T2 or greater disease was 0.806 (95% CI 0.780 to 831) and 0.864 (95% CI 0.839 to 0.890), respectively. For each NMP22 cutoff NMP22 had higher sensitivity for detecting grade III and stage T2 or greater bladder transitional cell carcinoma than for detecting any cancer. No optimal cutoffs for detecting any or aggressive bladder transitional cell carcinoma could be derived based on NMP22 values. CONCLUSIONS: There is a substantial degree of heterogeneity in the diagnostic performance of NMP22 applied to populations from different institutions. There is no clearly defined NMP22 cutoff but there is a continuum of risk for recurrence and progression.

Adult↗

High molecular mass phosphoproteins in the rat liver nuclear matrix identification of a prominent 110,000 Dalton species.

Purified rat liver nuclei were labelled in vitro in the presence of (32P) ATP and submitted to sequential extraction with DNAse, 0.4 or 2.0 M NaCl and Triton X-100. The residual or matrix structures contained 8-10 phosphoproteins between 76 and 260 kd including a triplet of major bands with 110, 117 and 128 kd. The 110 kd species was purified by chromatography on oligo(dT)-cellulose. It was shown to be identical with the 110 kd phosphoprotein of rat liver or Morris hepatoma free polyribosomes using the technique of limited digestion with S. aureus protease V 8.

Animals↗