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Cinzia Mazzini, Pamela Pinzani, Francesca Salvianti, Daniela Massi, Giulia Pieretti, Giacomo Abbruzzese, Matteo Giuntoli, Mario Pazzagli, Ugo Menchini; Pheno-Genotypic Identification of Circulating Tumor Cells in Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1456.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal Melanoma is the most common intraocular tumor.Patients with primary uveal melanoma show tumor cell dissemination and formation of metastases through the bloodstream.Pheno-genotypic markers can be used for the early detection of disseminated tumor cells.Analysis of circulating tumor cells (CTC) in the peripheral blood provides clinically useful information.Isolation by size of epithelial tumor cells(ISET/ScreenCell)is a direct method for CTC identification,in which tumor cells are collected by filtration.Upon isolation,the identity of tumor cells as melanoma cells can be supported by immunohistochemistry and their presence indirectly supported by mRNA tyrosinase levels.Recently a four color FISH probe assay has been devised by Abbot Molecular Laboratories for the identification of chromosomal abnormalities in melanocytic lesions.We investigated the presence of ISET-isolated CTC and we performed immunohistochemical and FISH analysis.
41 patients were longitudinally investigated over 5 years. mRNA tyrosinase levels were assessed by RT-PCR.Results were correlated with the number of CTC assessed by ISET.The identity of cells,trapped in filters and stained with H&E, as CTC was supported by positivity for immunohistochemical markers (S-100protein,Tyrosinase,MART-1/Melan A).The presence of chromosomal abnormalities of CTC was evaluated by FISH.
Increased mRNA tyrosinase levels were found in 20 of 41 patients and correlated with tumor dimensions (p<0,01),disease free and overall survival (p<0,05).CTC were isolated by ISET in 5/16 patients and the direct correlation between CTC values and tyrosinase levels was found.Immunohistochemical analysis confirmed the identification of tumor cells as melanoma cells.FISH analysis confirmed the presence of genetical abnormalities in CTC.
Tyrosinase assay by RT-PCR is a non-invasive method for monitoring tumor progression in uveal melanoma. mRNA tyrosinase levels can be taken as an indirect parameter correlated to the number of CTC isolated from blood by ISET.FISH analysis may bring new tools for CTC characterization. Our results indicate the need for larger prospective studies with purposes including whether CTC may predict the behaviour of the entire pool of occult tumor cells and drug sensitivity of the corresponding tumor tissue.
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