Matrix metalloproteinase MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 in bladder carcinoma
1University of Oulu, Faculty of Medicine, Institute of Clinical Medicine, Department of Oncology and Radiotherapy
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|Persistent link:|| http://urn.fi/urn:isbn:9789514288746
|Publish Date:|| 2008-10-21
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic Dissertation to be presented, with the assent of the Faculty of Medicine of the University of Oulu, for public defence in Auditorium 7 of Oulu University Hospital, on October 31st, 2008, at 12 noon
Docent Hanna Mäenpää
Professor Teuvo Tammela
Bladder cancer when superficial has a good prognosis but it has a high recurrence risk and about 10–15% of the superficial carcinomas will progress into muscle invasive or metastatic type. The most powerful factor for predicting the behavior of bladder carcinoma is the stage of the tumor. Invasion to the lamina propria increases the risk of recurrence and progress to muscle-invasive tumor. Also grade of the tumor and tumor multiplicity associates with high risk for recurrence. New markers are still needed to find those patients who need more and better treatments to avoid the recurrence and progress. The need for new non-invasive markers to diminish the need for frequent cystoscopy in follow-up is also obvious.
Gelatinases MMP-2 and MMP-9 are known to associate to tumor invasion and progression. Also their tissue inhibitors TIMP-1 and TIMP-2 take part in these diversified processes and metastasis formation. In the present work the expression and clinical value of gelatinases MMP-2 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 were evaluated in bladder carcinoma. Primary tissue samples of 121 patients were analyzed for expression of MMP-2 and/or MMP-9 using immunohistochemistry. The serum samples of 87 patients who were treated in the Oncology Department of Oulu University Hospital were collected and studied with ELISA. The control group consisted of 44 healthy volunteers.
Overexperssion of MMP-2 protein correlated significantly to disease-specific survival and showed an independent prognostic value as a biomarker. High MMP-9 expression instead correlated to favorable overall survival of bladder cancer patients. Circulating proMMP-2, TIMP-2 and MMP-2:TIMP-2 complex levels were lower in cancer patients than in healthy volunteers in control group. High levels of all these three markers correlated with better prognosis in bladder cancer patients.
Acta Universitatis Ouluensis. D, Medica
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