Detection and Characterization of Circulating Tumor Cells in Patients with Merkel Cell Carcinoma
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Detection and Characterization of Circulating Tumor Cells in Patients with Merkel Cell Carcinoma. / 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.
in: CLIN CHEM, Jahrgang 65, Nr. 3, 03.2019, S. 462-472.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Detection and Characterization of Circulating Tumor Cells in Patients with Merkel Cell Carcinoma
AU - Riethdorf, Sabine
AU - Hildebrandt, Lina
AU - Heinzerling, Lucie
AU - Heitzer, Ellen
AU - Fischer, Nicole
AU - Bergmann, Sonja
AU - Mauermann, Oliver
AU - Waldispühl-Geigl, Julie
AU - Coith, Cornelia
AU - Schön, Gerhard
AU - Peine, Sven
AU - Schuler, Gerold
AU - Speicher, Michael R
AU - Moll, Ingrid
AU - Pantel, Klaus
N1 - © 2018 American Association for Clinical Chemistry.
PY - 2019/3
Y1 - 2019/3
N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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, P = 0.030; >1, P < 0.020; and ≥5 CTCs/7.5 mL, P < 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 (P = 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.CONCLUSIONS: 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.
AB - BACKGROUND: 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.METHODS: 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.RESULTS: 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, P = 0.030; >1, P < 0.020; and ≥5 CTCs/7.5 mL, P < 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 (P = 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.CONCLUSIONS: 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.
KW - Journal Article
U2 - 10.1373/clinchem.2018.297028
DO - 10.1373/clinchem.2018.297028
M3 - SCORING: Journal article
C2 - 30626636
VL - 65
SP - 462
EP - 472
JO - CLIN CHEM
JF - CLIN CHEM
SN - 0009-9147
IS - 3
ER -
