Noninvasive diagnosis of bladder cancer by detection of matrix metalloproteinases (MMP-2 and MMP-9) and their inhibitor (TIMP-2) in urine.
OBJECTIVE
TIMPs control the activity of MMPs, one of the key molecules for tumor invasion and metastasis. The aim of this study was to assess the usefulness of MMP-2 and MMP-9 in relation to their inhibitor (TIMP2) as noninvasive diagnostic tests for bilharzial bladder cancer.


METHODS
Voided urine samples were provided from 244 subjects (154 bladder cancer [136 bilharzial]; 60 benign urologic disorders; 30 healthy volunteers). Urine sediment was used for cytology, and the supernatant for estimation of MMPs and TIMP-2 by ELISA and gelatin zymography.


RESULTS
The best cut-off values for the investigated markers were determined by ROC curve. Positivity rates and median levels for MMP-2, MMP-9, TIMP-2, MMP-2/TIMP-2, and MMP-9/TIMP-2 showed significant difference among the three investigated groups (p<0.001). MMP-9 and MMP-2/TIMP-2 were related to pathologic type, MMP-2/TIMP-2 was inversely related to the grade, and MMP-9/TIMP-2 was related to bilharziasis (p<0.05). MMP zymography results were comparable to those from ELISA.


CONCLUSIONS
The sensitivity and specificity of MMP zymography, MMP-9/TIMP-2 ratio, and MMP-2/TIMP2 ratio were superior among all investigated parameters; furthermore, combined testing of cytology with them improves the sensitivity even in superficial and low-grade tumors.
Eissa
Sanaa
S
Oncology Diagnostic Unit, Medical Biochemistry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. sanaa_eissa@hotmail.com
Ali-Labib
Randa
R
Swellam
Menha
M
Bassiony
Manal
M
Tash
Fathy
F
El-Zayat
Tarek Mostafa
TM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000201:enzymology; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000201:enzymology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000652:urine*; D020780:Matrix Metalloproteinase 9 / Q000652:urine*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012720:Severity of Illness Index; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000201:enzymology
D014408:Biomarkers, Tumor; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9