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D. C. Reed, G. Boru, F. H. Davidorf, M. H. Abdel-Rahman; Multi-Marker Testing for Circulating Uveal Melanoma Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3382.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma (UM) spreads hematogenously to the liver in about 35% of cases, even with treatment of the primary tumor. Detection of circulating UM cells in peripheral blood could have implications for diagnosis, treatment, prognosis, and/or follow up of UM patients.
Tumor markers that are expressed at high levels in UM and low or zero levels in peripheral blood mononuclear cells were identified from the literature and the UniGene database. Next, sensitivity and specificity testing were performed on these markers using reverse transcriptase PCR (RT-PCR) techniques and the three best markers were retained in the study. Finally, peripheral blood samples from 46 UM patients and 30 controls were assayed for these tumor markers. Five of the UM patients included had metastatic disease at the time of blood draw.
The genes identified by literature and UniGene search were: TYR, MLANA, MET, FABP5, KIT, ENPP2, CDH1, MCAM, and MIA. Sensitivity and specificity testing showed that RT-PCR techniques using TYR and MLANA were able to detect 2 melanoma cells/ml blood, the most dilute sample tested. The next best marker, MET, had a sensitivity of 800-2600 cells/ml. RT-PCR techniques were then employed on peripheral blood samples from UM patients and controls. TYR was not detected in controls, but was detected in the peripheral blood of 3/46 UM patients. MLANA was detected in 28/30 controls and 45/46 UM patients. Using a cutoff value, only one UM patient was considered positive for MLANA, and this individual was also one of the TYR-positive patients. MET was detected in all controls and patients and showed wide variability of expression in both groups. Only one out of the five patients with metastatic disease at the time of blood draw had detectable levels of TYR in his/her peripheral blood.
Our data suggests that RT-PCR techniques using TYR are highly sensitive and specific for detection of circulating UM cells. However, it appears that a single blood draw will not reliably contain a circulating UM cell, even in a patient with known metastases. Our data also suggests that MLANA, MCAM and MIA - all previously suggested as potential circulating melanoma cell markers - are not specific for detection of circulating UM cells due to the high background expression of these genes in peripheral blood mononuclear cells.
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