May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Differential Expression of Tissue Inhibitor of Matrix-metalloproteinases 3 in Uveal Melanoma
Author Affiliations & Notes
  • G.C. Nareyeck
    Ophthalmology, University of Essen, Essen, Germany
  • F. Tschentscher
    Human Genetics, University of Essen, Essen, Germany
  • M. Zeschnigk
    Human Genetics, University of Essen, Essen, Germany
  • D. von der Haar
    Human Genetics, University of Essen, Essen, Germany
  • H. Schilling
    Human Genetics, University of Essen, Essen, Germany
  • G. Anastassiou
    Human Genetics, University of Essen, Essen, Germany
  • Footnotes
    Commercial Relationships  G.C.W. Nareyeck, None; F. Tschentscher, None; M. Zeschnigk, None; D. von der Haar, None; H. Schilling, None; G. Anastassiou, None.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1543. doi:
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      G.C. Nareyeck, F. Tschentscher, M. Zeschnigk, D. von der Haar, H. Schilling, G. Anastassiou; Differential Expression of Tissue Inhibitor of Matrix-metalloproteinases 3 in Uveal Melanoma . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1543.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: The tissue inhibitor of matrix-metalloproteinases 3 (TIMP-3) is a factor with inhibitory effect upon matrix metalloproteinases (MMPs) like the other TIMPs. Among TIMPs only TIMP-3 is stored in the extracellular matrix (ECM) mainly by heparan sulphate-proteoglycans. The diverse possibilities for interactions between MMPs and TIMPs in terms of matrix degradation and MMP-activation has been only partially investigated in uveal melanoma and some reports found an association between MMPs and patient survival. Recently TIMP-3 is thought to be involved even in apoptosis. In the present study the expression of TIMP-3 and its association with genetical and histopathological features was investigated. Methods: Twenty primary uveal melanomas were collected immediately after surgery and RNA was isolated for microarray analysis (Affymetrix, HG-U95Av2). Using a Wilcoxon rank test on the basis of chromosome 3 status (assessed with microsatellite analysis) several differentially expressed genes were identified. Immunohistochemistry, including antigen retrieval, was used to localise TIMP-3 (Acris, monoclonal antibody 136-13H4) in paraffin sections of enucleated human eyes containing the same primary tumors investigated by microarray analysis. Results: The mRNA expression level of TIMP-3 was associated with the chromosome 3 status. Tumors with monosomy 3 showed very low levels of expression whereas tumors with disomy 3 were expressing high levels of TIMP-3 (p=0.002). These results could be tendencially confirmed by the immunohistochemical detection of TIMP-3. There was no further association between TIMP-3 expression and histopathological or genetical features (tumor location, histological type, vascular patterns, aberrations in chromosome 6 and 8). Conclusions: TIMP-3 is differentially expressed among uveal melanomas. The absence of TIMP-3 in tumors with monosomy 3, which are aggressive and highly metastatic tumors, may indicates a possible role of TIMP-3 in the dissemination of uveal melanoma.

Keywords: tumors • uvea • choroid 
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