Sabine Riethdorf1, Lina Hildebrandt2, Lucie Heinzerling3, Ellen Heitzer4, Nicole Fischer5, Sonja Bergmann6, Oliver Mauermann6, Julie Waldispühl-Geigl4, Cornelia Coith6, Gerhard Schön7, Sven Peine8, Gerold Schuler3, Michael R Speicher4, Ingrid Moll2, Klaus Pantel6. 1. Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; s.riethdorf@uke.de. 2. Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 3. Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany. 4. Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, University of Graz, Graz, Austria. 5. Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 6. Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 7. Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 8. Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Abstract
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.
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.
Authors: Linde M van Veenendaal; Eduardo Bertolli; Catharina M Korse; W Martin C Klop; Margot E T Tesselaar; Alexander C J van Akkooi Journal: Ann Surg Oncol Date: 2020-06-11 Impact factor: 5.344
Authors: T Gambichler; S Said; N Abu Rached; C H Scheel; L Susok; R Stranzenbach; J C Becker Journal: J Cancer Res Clin Oncol Date: 2022-01-31 Impact factor: 4.322