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M.C. Madigan, E.E. Cornish, R.M. Conway, R. Natoli, J.M. Provis; FGFR4 Expression in Human Choroidal Melanoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2217.
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Fibroblast growth factors (FGFs) are involved in cell differentiation, angiogenesis and tumour growth, mediated by binding to high–affinity tyrosine kinase receptors [FGFR1–FGFR6] and extracellular matrix components. Misexpression or mutation of FGFR4 has been reported in various tumours, and may be important in growth and invasion of established tumors. In this study we investigated the expression of FGFR4 mRNA and protein in uveal melanoma cell lines, primary choroidal melanocytes and a series of primary choroidal melanomas.
FGFR4 expression (protein and mRNA) was assessed in uveal melanoma cell lines (OCM–1, –3, –8, OMM–1, 92–1 and Mel202) using immunocytochemistry, flow cytometry, immunoblotting and diagnostic RT–PCR. Sections of whole eyes with choroidal melanomas of mixed spindle/epithelioid morphology (n=23) were immunolabelled for FGFR4 using a polyclonal antibody to the carboxy terminus of FGFR4.
For melanoma cell lines, immunoblotting showed positive bands of ∼110kDa and 125kDa indicating wild–type FGFR4 protein. Flow cytometry and immunocytochemistry confirmed FGFR4 protein expression in melanoma cell lines. FGFR4 mRNA was also detected in all uveal melanoma cell lines. For choroidal melanomas, 5/23 displayed moderate to intense cytoplasmic immunolabeling of individual cells throughout tumors; 4/23 showed low level FGFR4 immunolabeling and in 14/23 tumors FGFR4 immunolabeling was not obvious.
The intense cytoplasmic FGFR4 immunolabeling of scattered cells in some primary choroidal melanomas was similar to that seen in pituitary tumors with mutant FGFR4 protein. FGFR4 (and other FGFs) may be involved in the local progression of some choroidal melanomas.
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