Differential Expression of Tissue Inhibitor of Matrix Metalloproteinases 3 in Uveal Melanoma

Vol. 37, No. 1, 2005

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Original Paper

Differential Expression of Tissue Inhibitor of Matrix Metalloproteinases 3 in Uveal Melanoma
Gordon Nareyeck^a, Michael Zeschnigk^b, Daniela von der Haar^a, Harald Schilling^a, Norbert Bornfeld^a, Gerasimos Anastassiou^a

Departments of
^aOphthalmology and
^bHuman Genetics, Universitätsklinikum Essen, Essen, Germany

Address of Corresponding Author

Ophthalmic Res 2005;37:23-28 (DOI: 10.1159/000082940)

Key Words

Uveal melanoma
Tissue inhibitor of matrix metalloproteinases 3
Gene expression analysis
Chromosome 3
Immunohistochemistry

Abstract

Based on gene profiling, two entities of uveal melanomas exist. So far, these two entities can be distinguished by the chromosome 3 status which strongly associates with the metastatic potential of the tumours. Reorganization of the extracellular matrix is one of the steps towards dissemination of tumour cells. In the present study, we examined the tissue inhibitor of matrix metalloproteinases (TIMP) 3 expression in 19 uveal melanomas and compared the results with histopathological and genetic features. The expression level of TIMP-3 mRNA as determined by microarray analysis was associated with the chromosome 3 status of the tumour (p = 0.003). All tumours with disomy 3 showed moderate to high expression of TIMP-3 mRNA, whereas TIMP-3 was highly expressed in one tumour, less expressed in 3 tumours and absent in the remaining 6 tumours with monosomy 3. Immunohistochemistry for TIMP-3 was positive in 9/19 tumours, but only in 3 tumours were more than 5% of the tumour cells stained positive. There was no association between immunohistochemical detection of TIMP-3 and chromosome 3 status. In tumours with disomy 3, we found none or very few TIMP-3-positive cells though the mRNA level was high which indirectly postulates posttranscriptional problems in protein biosynthesis in this entity of uveal melanomas. There was a trend between TIMP-3 protein expression and both cell type (p = 0.11) and presence of loops and/or networks (p = 0.06) in tumour which may indicate a role of TIMP-3 in the biology of uveal melanoma.

Author Contacts

Dr. Gordon Nareyeck
Augenklinik, Universitätsklinikum Essen
Hufelandstrasse 55
DE-45122 Essen (Germany)
Tel. +49 201 7234534, Fax +49 201 7235748, E-Mail gordon.nareyeck@uni-essen.de

Article Information

Received: December 30, 2003
Accepted after revision: September 21, 2004
Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 2, Number of References : 16

Medline Abstract (ID 15637418)

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