title: Differential expression of tissue inhibitor of matrix metalloproteinases 3 in uveal melanoma.
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.
authors.affiliation: Department of Ophthalmology, Universitatsklinikum Essen, Essen, Germany. gordon.nareyeck@uni-essen.de
authors.forename: Gordon
authors.initials: G
authors.lastname: Nareyeck
authors.forename: Michael
authors.initials: M
authors.lastname: Zeschnigk
authors.forename: Daniela
authors.initials: D
authors.lastname: von der Haar
authors.forename: Harald
authors.initials: H
authors.lastname: Schilling
authors.forename: Norbert
authors.initials: N
authors.lastname: Bornfeld
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Anastassiou
mesh_terms: D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009006:Monosomy / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3