title: Circulating tumor cells in patients with testicular germ cell tumors.
abstract: OBJECTIVE
  Germ cell tumors (GCTs) represent the most frequent malignancies among young men, but little is known about circulating tumor cells (CTCs) in these tumors. Considering their heterogeneity, CTCs were investigated using two independent assays targeting germ cell tumor and epithelial cell-specific markers, and results were correlated with disease stage, histology, and serum tumor markers.
  
  
  METHODS
  CTCs were enriched from peripheral blood (n = 143 patients) and testicular vein blood (TVB, n = 19 patients) using Ficoll density gradient centrifugation. For CTC detection, a combination of germ cell tumor (anti-SALL4, anti-OCT3/4) and epithelial cell-specific (anti-keratin, anti-EpCAM) antibodies was used. In parallel, 122 corresponding peripheral blood samples were analyzed using the CellSearch system.
  
  
  RESULTS
  In total, CTCs were detected in 25 of 143 (17.5%) peripheral blood samples, whereas only 11.5% of patients were CTC-positive when considering exclusively the CellSearch assay. The presence of CTCs in peripheral blood correlated with clinical stage (P < 0.001) with 41% of CTC positivity in patients with metastasized tumors and 100% in patients with relapsed and chemotherapy-refractory disease. Histologically, CTC-positive patients suffered more frequently from nonseminomatous primary tumors (P < 0.001), with higher percentage of yolk sac (P < 0.001) and teratoma (P = 0.004) components. Furthermore, CTC detection was associated with elevated serum levels of α-fetoprotein (AFP; P = 0.025), β-human chorionic gonadotropin (βHCG; P = 0.002), and lactate dehydrogenase (LDH; P = 0.002). Incidence and numbers of CTCs in TVB were much higher than in peripheral blood.
  
  
  CONCLUSIONS
  The inclusion of germ cell tumor-specific markers improves CTC detection in GCTs. CTCs occur frequently in patients with more aggressive disease, and there is a gradient of CTCs with decreasing numbers from the tumor-draining vein to the periphery.
authors.affiliation: Authors' Affiliations: Departments of Tumour Biology.
authors.forename: Paulina
authors.initials: P
authors.lastname: Nastały
authors.affiliation: Urology, and Department of Urology, Federal Armed Forces Hospital, Hamburg; and.
authors.forename: Christian
authors.initials: C
authors.lastname: Ruf
authors.affiliation: Department of Urology, Federal Armed Forces Hospital, Hamburg; and.
authors.forename: Pascal
authors.initials: P
authors.lastname: Becker
authors.affiliation: Authors' Affiliations: Departments of Tumour Biology.
authors.forename: Natalia
authors.initials: N
authors.lastname: Bednarz-Knoll
authors.affiliation: Authors' Affiliations: Departments of Tumour Biology.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Stoupiec
authors.affiliation: Authors' Affiliations: Departments of Tumour Biology.
authors.forename: Refik
authors.initials: R
authors.lastname: Kavsur
authors.affiliation: Urology, and.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Isbarn
authors.affiliation: Department of Urology, Federal Armed Forces Hospital, Hamburg; and.
authors.forename: Cord
authors.initials: C
authors.lastname: Matthies
authors.affiliation: Department of Urology, Federal Armed Forces Hospital, Hamburg; and.
authors.forename: Walter
authors.initials: W
authors.lastname: Wagner
authors.affiliation: Federal Armed Forces Hospital, Department of Urology, Berlin, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Höppner
authors.affiliation: Urology, and.
authors.forename: Margit
authors.initials: M
authors.lastname: Fisch
authors.affiliation: Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, University Medical Centre Hamburg-Eppendorf;
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.affiliation: Urology, and.
authors.forename: Sascha
authors.initials: S
authors.lastname: Ahyai
authors.affiliation: Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, University Medical Centre Hamburg-Eppendorf;
authors.forename: Friedemann
authors.initials: F
authors.lastname: Honecker
authors.affiliation: Authors' Affiliations: Departments of Tumour Biology.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.affiliation: Authors' Affiliations: Departments of Tumour Biology, pantel@uke.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002881:Chromosomes, Human, Pair 12; D006801:Humans; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D013736:Testicular Neoplasms / Q000235:genetics / Q000473:pathology*; D014314:Trisomy / Q000473:pathology; D055815:Young Adult