Prognostic value of membrane type 1 and 2 matrix metalloproteinase expression and gelatinase A activity in bladder cancer.
OBJECTIVE
To analyze the behavior of matrix metalloproteinases (MMPs) in their active state in patients with bladder cancer.


METHODS
A retrospective study of 50 patients with localized bladder cancer who underwent tumor resection between June 2006 and June 2007 at the National Cancer Institute in Cairo, Egypt was carried out. Tissue samples were collected and the expression of membrane type 1 (MT1) and type 2 (MT2) MMPs was determined by Western blotting. Gelatinase A (MMP-2) activity was estimated by zymographic analysis in tissue samples of each patient and the values were correlated with clinical tumor stage and lymph node status.


RESULTS
The behavior of MMP-2 showed statistical significance in 90% of tumor tissues compared with 22% of adjacent normal tissues (p<0.001). MT1-MMP was expressed in 88% of tumor tissues compared with 24% of normal tissues (p<0.001); MT2-MMP was expressed in 74% of tumor tissues compared with 12% of normal tissues (p<0.001). While there was a highly significant association between MMP-2 activity and MT1-MMP expression in tumor tissues (p<0.001), there was a moderately significant association between MMP-2 activity and MT2-MMP expression (p=0.018). The results also revealed an association between MT1-MMP and MT2-MMP expression in tumor tissues (p<0.001). MMP-2 activity and MT2-MMP expression in tumor tissues were statistically associated with high tumor stage (p=0.039 and p=0.014, respectively), while the expression of MT1-MMP showed no association with tumor stage (p=0.139).


CONCLUSIONS
MMP-2 activity is associated with an increase in MT2-MMP expression and with lymph node metastasis. No association was found between MT1-MMP expression and lymph node metastasis.
Mohammad
Mohammad A
MA
Biochemistry and Molecular Biology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Ismael
Naglaa R
NR
Shaarawy
Sabry M
SM
El-Merzabani
Mahmoud M
MM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D053517:Matrix Metalloproteinase 15 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
C507098:MMP15 protein, human; D053517:Matrix Metalloproteinase 15; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14