Abstract
Simple SummaryCirculating tumor cells (CTCs) originating from cutaneous melanoma patients have been studied for several decades as surrogates for real-time clinical status and disease outcomes. Here, we will review clinical studies from the last 15 years that assessed CTCs and disease outcomes for melanoma patients. Assessment of multiple molecular melanoma-associated antigen (MAA) markers by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was the most common assay allowing for the improvement of assay sensitivity, to address tumor heterogeneity, and to predict patient outcomes. Multicenter studies demonstrate the utility of CTC assays reducing the bias observed in single-center trials. Recent development of CTC enrichment platforms has provided reproducible methods. CTC assessment enables both multiple mRNAs and DNAs genomic profiling. CTC provides specific important translational information on tumor progression, prediction of treatment response, and survival outcomes for cutaneous melanoma patients.Circulating tumor cells (CTCs) have been studied using multiple technical approaches for interrogating various cancers, as they allow for the real-time assessment of tumor progression, disease recurrence, treatment response, and tumor molecular profiling without the need for a tumor tissue biopsy. Here, we will review studies from the last 15 years on the assessment of CTCs in cutaneous melanoma patients in relation to different clinical outcomes. The focus will be on CTC detection in blood samples obtained from cutaneous melanoma patients of different clinical stages and treatments utilizing multiple platforms. Assessment of multiple molecular melanoma-associated antigen (MAA) markers by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was the most common assay allowing for the improvement of assay sensitivity, tumor heterogeneity, and to predict patient outcomes. Multicenter studies demonstrate the utility of CTC assays reducing the bias observed in single- center trials. The recent development of CTC enrichment platforms has provided reproducible methods. CTC assessment enables both multiple mRNAs and DNAs genomic aberration profiling. CTC provides specific important translational information on tumor progression, prediction of treatment response, and survival outcomes for cutaneous melanoma patients. The molecular studies on melanoma CTCs have provided and may set standards for other solid tumor CTC analyses.
Highlights
Cutaneous melanoma arises from the transformation of skin melanocytes to melanoma cells, often related to damaging chronic sunlight UV light exposure [1]
A review of original articles analyzing the prognostic value of Circulating tumor cells (CTCs) in cutaneous melanoma patients in the last 15 years was performed by searching the PubMed database
The analysis of baseline blood samples did not show clinical significance in this study, the number of melanoma-associated antigen (MAA) CTC markers expressed revealed that disease-free survival (DFS) and distant-disease-free survival (DDFS) were significantly worse for patients with ≥1 marker detected at any point during follow-up compared to patients with negative results
Summary
Cutaneous melanoma arises from the transformation of skin melanocytes to melanoma cells, often related to damaging chronic sunlight UV light exposure [1]. We will describe the recent developments of CTC assessment in cutaneous melanoma patients, and the different approaches applied to clinical studies analyzing prognostic information from the last 15 years. Sensitivity and accuracy in CTC detection are associated with critical factors during blood collection procedures (including methods of collection, isolation, platforms utilized for purification), data analyses (molecular assay readouts, standardization, reproducibility, specificity of biomarkers for CTCs, CTCs quantification, and results interpretation), and the in-depth quality of the clinical data available (tumor staging, the time of blood draw, and patient follow-up). We use Cell-Free DNA BCT® tubes (Streck Corporate, NE, USA) which preserve intact CTCs for up to seven days at room temperature The utility of this approach is in multicenter studies where blood can be shipped to a single centralized laboratory site and assessed several days later. This review describes the findings of the CTC assays developed in recent years under clinical settings, and the clinical interpretations found in cutaneous melanoma patients
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