Abstract
Metastatic melanoma is one of the most aggressive and drug-resistant cancers with very poor overall survival. Circulating melanoma cells (CMCs) detection was described since 1991 and numerous studies have been reported. However, there is no general consensus of clinical utility of CMC detection, largely due to conflicting results from heterogeneous studies and discrepancies in methods of detection between studies. Here, we chose to explore the possibility of using a newly developed S100-EPISPOT assay to detect viable CMCs in a homogeneous population of metastatic melanoma patients and compared these results with those obtained with the CellSearch® CMC kit. This study reveals that the sensitivity of the S100-EPISPOT is significantly higher than that of the CellSearch®. On this cohort, 48% had ≥ 2 CMCs by using the S100-EPISPOT whereas only 21% had ≥ 2 CMCs detected by the CellSearch® (p=0.0114). Regarding the prognostic value of the CMC with both assays, only the CellSearch®results showed a significant association with the overall survival (p=0.006). However, the high sensitivity (48%) of the newly developed S100-EPISPOT would be of interest to study the impact of this analysis in a cohort of non-metastatic melanoma patients to evaluate the ability of this functional assay for early detection of tumor relapse or monitoring therapy response.
Highlights
S100-EPISPOT: a new tool to detect viable circulating melanoma cells L Cayrefourcq1, A De Roeck3, C Garcia2, P Stoebner2, F Fichel2, F Garima1, F Perriard3, J Daures3, L Meunier2 and C Alix-Panabieres1 1 Laboratory of Rare Circulating Cells, University Medical Centre of Montpellier, Montpellier, France, 2 Department of Dermatology, Caremeau University Hospital, Nımes, France and 3 UPRES EA2415, Montpellier University, Montpellier, France Metastatic melanoma is one of the most aggressive and drug-resistant cancers with very poor overall survival
We chose to explore the possibility of using a newly developed S100-EPISPOT assay to detect viable Circulating melanoma cells (CMCs) in a homogeneous population of metastatic melanoma patients and compared these results with those obtained with the CellSearchÒ CMC kit
This study reveals that the sensitivity of the S100EPISPOT is significantly higher than that of the CellSearchÒ
Summary
There was globally more epidermal proliferation in the presence of UVB irradiation, proliferating cells were concentrated within 60um of hair follicle openings and clones distant from hair follicles harboured label retaining cells suggesting their relative slow cycling behaviour. In a UVB inducible murine BCC model (K14Cre/ER : Ptch1lox/+ mice), keratin17 expressing groups of epidermal cells reflecting hedgehog pathway activation through loss of the second ptch1 allele were evenly distributed across dorsal skin, they were larger in size if attached to hair follicles.
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