Comparative study of NMP-22, telomerase, and BTA in the detection of bladder cancer.
OBJECTIVE
The diagnostic efficacy of Nuclear Matrix Protein-22 (NMP-22), bladder tumor antigen (BTA TRAK), and telomerase activity was evaluated in urine in a trial to assess their value in the detection of bladder cancer and to compare it to that of routine urine cytology.


METHODS
The study included 46 newly diagnosed bladder cancer patients, diagnosed by cystoscopy and histopathological typing, in addition to 20 patients with benign bladder lesions and 20 healthy age and sex matched volunteers as a control group. Fifty percent of the cancer patients (23/46) had proven bilharzial history. Most patients (27/46) had transitional cell carcinoma (TCC), 17/46 had squamous cell carcinoma (SCC), while only 2 patients had adenocarcinoma. A single freshly voided urine sample (approximately 100ml) was collected from each patient and control subject and aliquoted for each test. All assays were conducted according to the manufacturer's guidelines and the results were compared to those of urine cytology.


RESULTS
The optimal cutoffs for NMP-22, BTA and telomerase activity as calculated by ROC curves were 12.1 U/ml, 78 U/ml, 0.48 (Ratio) respectively. The levels of the three parameters were significantly higher in the malignant group compared to either the benign group or normal controls, (p<0.001) and the positive rates were also higher in the malignant group for all 3 parameters. The overall sensitivity of urine cytology, NMP-22, BTA and telomerase was 54.3%, 91.3%, 100% and 80.4% respectively. For bilharzial cancer bladder respective sensitivities were 69.6%, 95.6%, 100% and 73.9%, while for nonbilharzial cancer bladder the respective sensitivities were 39.1%, 87%, 100% and 87%. The overall specificities with urine cytology, NMP-22, BTA and telomerase was 100%, 87.5%, 92.5% and 95.0%, respectively. Combined sensitivity of voided urine cytology with one or more of the 3 biomarkers, or the use of these biomarkers in double or triple combinations gave higher positivity than each biomarker alone.


CONCLUSIONS
BTA showed the highest sensitivity in all the studied parameters in the bladder cancer group, bilharzial bladder cancer subgroup, and non bilharzial bladder subgroup, (100%), while the highest specificity was recorded with urine cytology (100%), followed by telomerase (95%), then BTA (92.5%), and lastly NMP- 22 (87.5%). Use of markers in combination with cytology, or in a panel, improved the sensitivity, and specificity.
Abd El Gawad
Iman A
IA
The Department of Clinical & Chemical Pathology, NCI, Cairo University.
Moussa
Heba S
HS
Nasr
Maha I
MI
El Gemae
Emad H
EH
Masooud
Amr M
AM
Ibrahim
Ibrahim K
IK
El Hifnawy
Niveen M
NM
D000230:Adenocarcinoma / Q000175:diagnosis / Q000652:urine; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000652:urine*; D014408:Biomarkers, Tumor / Q000652:urine*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000652:urine*; D012553:Schistosomiasis haematobia / Q000150:complications; D019098:Telomerase / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000469:parasitology / Q000652:urine*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C112999:bladder tumor-associated antigen; C100379:nuclear matrix protein 22; D019098:Telomerase