Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells

• Published in: British journal of cancer Vol. 122; no. 7; pp. 1059 - 1067
• Main Authors: Aya-Bonilla, Carlos Alberto, Morici, Michael, Hong, Xin, McEvoy, Ashleigh Cavell, Sullivan, Ryan Joseph, Freeman, James, Calapre, Leslie, Khattak, Muhammad Adnan, Meniawy, Tarek, Millward, Michael, Ziman, Mel, Gray, Elin Solomonovna
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2020; Nature Publishing Group
• Subjects: 692/4028/67/1813/1634; 692/4028/67/1857; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Cell Line, Tumor; Drug Resistance; Epidemiology; Female; Humans; Immunocytochemistry; Male; Medical prognosis; Melanoma; Melanoma - pathology; Metastases; Metastasis; Microfluidics; Molecular Medicine; Neoplastic Cells, Circulating - pathology; Oncology; Patients; Pharmacodynamics; Polymerase chain reaction; Prognosis; Transcription; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-020-0750-9

Background Circulating tumour cells (CTCs) can be assessed through a minimally invasive blood sample with potential utility as a predictive, prognostic and pharmacodynamic biomarker. The large heterogeneity of melanoma CTCs has hindered their detection and clinical application. Methods Here we compared two microfluidic devices for the recovery of circulating melanoma cells. The presence of CTCs in 43 blood samples from patients with metastatic melanoma was evaluated using a combination of immunocytochemistry and transcript analyses of five genes by RT-PCR and 19 genes by droplet digital PCR (ddPCR), whereby a CTC score was calculated. Circulating tumour DNA (ctDNA) from the same patient blood sample, was assessed by ddPCR targeting tumour-specific mutations. Results Our analysis revealed an extraordinary heterogeneity amongst melanoma CTCs, with multiple non-overlapping subpopulations. CTC detection using our multimarker approach was associated with shorter overall and progression-free survival. Finally, we found that CTC scores correlated with plasma ctDNA concentrations and had similar pharmacodynamic changes upon treatment initiation. Conclusions Despite the high phenotypic and molecular heterogeneity of melanoma CTCs, multimarker derived CTC scores could serve as viable tools for prognostication and treatment response monitoring in patients with metastatic melanoma.