Detection and Characterization of Circulating Tumor Cells in Patients with Merkel Cell Carcinoma

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 65; no. 3; pp. 462 - 472
• Main Authors: Riethdorf, Sabine, Hildebrandt, Lina, Heinzerling, Lucie, Heitzer, Ellen, Fischer, Nicole, Bergmann, Sonja, Mauermann, Oliver, Waldispühl-Geigl, Julie, Coith, Cornelia, Schön, Gerhard, Peine, Sven, Schuler, Gerold, Speicher, Michael R, Moll, Ingrid, Pantel, Klaus
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.03.2019
• Subjects: Aged; Apoptosis; B7-H1 Antigen - metabolism; Biomarkers; Blood circulation; Carcinoma, Merkel Cell - diagnosis; Carcinoma, Merkel Cell - metabolism; Cell Count - methods; Chromosome aberrations; Deoxyribonucleic acid; Disease; DNA; DNA, Viral - analysis; Female; Humans; Immune checkpoint; Immunotherapy; Kaplan-Meier Estimate; Ligands; Male; Medical prognosis; Merkel cell polyomavirus - genetics; Metastasis; Mortality; Neoplastic Cells, Circulating - metabolism; Neuroendocrine tumors; Patients; PD-L1 protein; Peripheral blood; Prognosis; Proportional Hazards Models; Prostate cancer; Regression analysis; Skin cancer; Studies; Survival; Tumor cells; Tumors
• ISSN: 0009-9147; 1530-8561; 1530-8561
• DOI: 10.1373/clinchem.2018.297028

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with increasing incidence and high mortality rates. MCC has recently become the subject of immune checkpoint therapy, but reliable biomarkers for estimating prognosis, risk stratification, and prediction of response are missing. Circulating tumor cells (CTCs) were detected in peripheral blood from patients with MCC by use of the CellSearch system. Moreover, CTCs of selected cases were characterized for Merkel cell polyomavirus (MCPyV), chromosomal aberrations, and programed death ligand 1 (PD-L1) production. Fifty-one patients were tested at first blood draw (baseline), and 16 patients had 2 or 3 consecutive measurements to detect CTCs. At baseline, ≥1 CTC (range, 1-790), >1, or ≥5 CTCs/7.5 mL were detected in 21 (41%), 17 (33%), and 6 (12%) patients, respectively. After a median follow-up of 21.1 months for 50 patients, detection of CTCs correlated with overall survival (≥1, = 0.030; >1, < 0.020; and ≥5 CTCs/7.5 mL, < 0.0001). In multivariate Cox regression analysis, the detection of ≥5 CTCs/7.5 mL adjusted to age and sex compared to that of <5 was associated with a reduced overall survival ( = 0.001, hazard ratio = 17.8; 95% CI, 4.0-93.0). MCPyV DNA and genomic aberrations frequently found in MCC tissues could also be detected in single CTCs. Analyzed CTCs were PD-L1 negative or only weakly positive. The presence of CTCs is a prognostic factor of impaired clinical outcome, with the potential to monitor the progression of the disease in real time. Molecular characterization of CTCs might provide new insights into the biology of MCC.