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A. Mohan, V. Nalini, M.P. Shanmugam, J. Biswas, S. Krishnakumar; Role of Matrix Metalloproteinases and Their Inhibitors in Retinoblastoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1107.
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Purpose: The spread of malignant neoplasms is closely associated with matrix and basement membrane degradation, mediated by various classes of proteolytic enzymes. Matrix metalloproteinases (MMPs) appear to have a key role in the sequence of events that lead to local invasion and metastasis.Tissue inhibitors of metalloproteinases (TIMPs) regulate MMP activity , controlling the breakdown of extracellular matrix components. The aim of this study was to examine the role of MMP–2, MMP–9, TIMP–1 and TIMP–2 in 60 archival retinoblastoma tumor samples (30 non–invasive tumors and 30 invasive tumors) and correlate with histological grade (invasiveness) and with proliferative index (Ki–67). Methods: Immunohistochemistry (Labeled streptavidin – biotin complex method) was performed to detect MMP–2,MMP–9, TIMP–1,TIMP–2 and Ki–67 proteins using monoclonal antibodies. Statistical analysis was done using non–parametric testing. Results: MMP–2, MMP–9,TIMP–1, TIMP–2 and Ki–67 were localized to the tumor cells. Among the 30 tumors with no invasion, MMP–2, was negative in 24 tumors, MMP–9 was negative in 24 tumors, TIMP–1 was negative in 28 tumors and TIMP2 negative in 19 tumors.Ki–67 index of > 50% was seen in 17 tumors with no invasion. Among the 30 tumors with invasion MMP–2 was postive in 23 tumors, MMP–9 was positive in 19 tumors, TIMP–1 positive in 23 tumors and TIMP–2 positive in 21 tumors. Ki–67 of > 50% was seen in 26 tumors with invasion. The expression of MMPs,TIMPs and the proliferative index was significantly higher in the invasive tumors as compared to the non–invasive tumors: MMP–2 (P<0.0001), MMP–9 (P<0.0001), TIMP–1 (P<0.0001) and TIMP–2 (P<0.001) and Ki–67 ( P<0.05). Conclusions: The expression of MMP–2, MMP–9, TIMP–1 and TIMP–2 was higher in tumors with invasion of choroid/optic nerve and proliferative index. Both MMPs and TIMPs have a key role in extracellular matrix invasion in retinoblastoma, largely through their elaboration by tumor cells.
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