Table 1.
Previous studies analyzing the value of CTCs in UM
| Title | Reference | Patient number | Technique used | Major findings |
|---|---|---|---|---|
| Detection of melanocytes from uveal melanoma in peripheral blood using the polymerase chain reaction | Tobal et al. [31], 1993 | UM patients (n = 6) | RT-PCR of tyrosinase mRNA | CTCs detected in 3 of 6 patients; CTC positive result preceded overt metastatic disease in 1 patient; limit of detection sensitivity of 10 cells/5 mL of blood |
| The detection of melanoma cells in peripheral blood by reverse transcription-polymerase chain reaction | Foss et al. [32], 1995 | UM patients (n = 36) | RT-PCR of tyrosinase mRNA | No patient sample was positive for CTCs; limit of detection sensitivity of 1 cell/mL of blood; CTCs detected in 2 of 31 control blood samples |
| Quantitative detection of circulating tumor cells in cutaneous and ocular melanoma and quality assessment by real-time reverse transcriptase-polymerase chain reaction | Keilholz et al. [37], 2004 | high-risk primary UM (n = 21); metastatic UM (n = 26) | real-time PCR of tyrosinase, MelanA/MART1, and gp 100 mRNA | mRNA of tyrosinase, MelanA/MART1, and gp 100 expressed in higher quantities and frequency in stage IV UM patients compared to earlier stages |
| Five-year results of prognostic value of tyrosinase in peripheral blood of uveal melanoma patients | Boldin et al. [34], 2005 | UM patients (n = 41); no metastasis at diagnosis | RT-PCR of tyrosinase mRNA | CTCs detected in 16 of 41 patients; 11 of the 16 CTC-positive patients became CTC-negative after therapy; CTC positivity correlated with 5-year survival; limit of detection sensitivity of 3 cells/5 mL of blood |
| Circulating tumor cells as prognostic factor for distant metastases and survival in patients with primary uveal melanoma | Schuster et al. [35], 2007 | high-risk primary UM (n = 110) | real-time PCR of tyrosinase and MelanA/MART1 mRNA | CTCs detected in 11 of 110 patients, with no associations with clinical features; presence of tyrosinase or MelanA/MART1 transcripts was prognostic for metastasis and survival |
| Identification of circulating malignant cells and its correlation with prognostic factors and treatment in uveal melanoma. A prospective longitudinal study | Callejo et al. [36], 2007 | primary UM (n = 30) | nested RT-PCR of tyrosinase and MelanA mRNA | CTCs detected in 29 of 30 patients during the follow-up period; CTC presence was detected regardless of tumor size or time after treatment; limit of detection sensitivity of 10 cells/2 mL of blood |
| Tyrosinase mRNA levels in the blood of uveal melanoma patients: correlation with the number of circulating tumor cells and tumor progression | Pinzani et al. [33], 2010 | UM patients (n = 41) | real-time PCR of tyrosinase mRNA | 20 of 41 patients were positive for tyrosinase mRNA; correlation found between tyrosinase mRNA levels and CTC counts suggest that tyrosinase could be used as an indirect measurement for CTC level |
| Visualization of circulating melanoma cells in peripheral blood of patients with primary uveal melanoma | Ulmer et al. [38], 2008 | primary UM (n = 52) | immunostaining based on MCSP expression | CTCs detected in 10 of 52 patients, and not in the controls; CTC presence associated with ciliary body invasion, advanced tumor stage, and anterior tumor location; limit of detection sensitivity of 1 cell/mL of blood |
| Circulating melanoma cells in peripheral blood of patients with uveal melanoma before and after different therapies and association with prognostic parameters: a pilot study | Suesskind et al. [39], 2011 | UM patients (n = 81) | immunostaining based on MCSP expression | various primary tumor therapies showed no significant impact on CTC number in circulation |
| Circulating tumor cells detection and counting in uveal melanomas by a filtration-based method | Mazzini et al. [27], 2014 | primary UM (n = 31); choroidal nevi (n = 10) | isolation by size of epithelial tumor cells | single CTCs or clusters of cells detected in 17 of 31 UM patients, while no CTCs detected in choroidal nevi patients; patients with<10 CTCs/10 mL blood had significantly worse DFS and OS; limit of detection sensitivity of 1 cell/mL of blood |
| Identification of circulating melanoma cells in uveal melanoma patients by dual-marker immunoenrichment | Tura et al. [26], 2014 | primary UM patients (n = 31) | immunomagnetic enrichment of NKI/C3- and NKI/beteb-positive cells; followed by immunostaining for NKI/C3 or MCSP | CTCs detected in 29 of 31 patients using dual-immunomagnetic enrichment assay for NKI/C3 and NKI/beteb; suggest that a combination of two antibodies instead of single antibody may be more efficient at detecting CTCs |
| Immunomagnetic detection of micro metastatic cells in bone marrow of uveal melanoma patients: a paradox | Eide et al. [40], 2015 | UM patients (n = 328) | immunodetection of MCSP | CTCs detected in 2% of the patient cohort |
| Analysis of monosomy-3 in immunomagnetically isolated circulating melanoma cells in uveal melanoma patients | Tura et al. [43], 2016 | primary UM patients (n = 44) | immuno-FISH assay to detect chromosome 3 | CTCs detected in 91% of the patients; 58% of detected CTCs were positive for monosomy 3, associated with advanced tumor stage |
| Detection of circulating melanoma cells in choroidal melanocytic lesions | Bande et al. [41], 2015 | choroidal nevus (n = 4); primary UM (n = 8) | CellSearch | 50% of UM patients had<1 CTC detected in their blood sample, while no CTCs were found in the nevi patients; no significant correlation was found between CTC detection and clinical parameters (largest basal diameter, tumor height) |
| Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma | Bidard et al. [23], 2014 | metastatic UM (n = 40) | CellSearch | CTCs detected in 12 of 40 patients; CTC levels associated with presence of miliary hepatic metastasis, metastasis volume, PFS, and OS |
| Arterial blood, rather than venous blood, is a better source for circulating melanoma cells | Terai et al. [44], 2015 | metastatic UM (n = 17) | CellSearch | CTCs detected with greater frequency (100%) and quantities in arterial compared to venous blood; no significant association was found between CTC count and tumor burden within the liver |
| Pilot study of circulating tumor cells in early-stage and metastatic uveal melanoma | Anand et al. [42], 2019 | primary UM (n = 20); metastatic UM (n = 19) | CellSearch | OS at 24 months significantly lower in CTC-positive vs.-negative early-stage UM; mean CTC count was higher in the metastatic group |
CTCs, circulating tumor cells; DFS, disease-free survival; OS, overall survival; PFS, progression-free survival; UM, uveal melanoma.