title: Treatment monitoring of patients with epithelial ovarian cancer using invasive circulating tumor cells (iCTCs).
abstract: OBJECTIVE
  Contemporary management of epithelial ovarian cancer (EOC) uses biomarkers to monitor response to therapy. This study evaluates the role of invasive circulating tumor cells (iCTCs) in monitoring EOC treatment in comparison with serum cancer antigen 125 (CA125).
  
  
  METHODS
  Molecular and microscopic analyses were used to identify seprase and CD44 as tumor progenitor (TP) markers. The iCTC flow cytometry assay was optimized using blood donated by 64 healthy donors, 49 patients with benign abdominal diseases and 123 EOC patients. Serial changes in iCTCs and CA125 were measured in 129 blood and 169 serum samples, respectively, from 31 EOC patients to assess their concordance during therapy and their relationship with risk of progressive disease (PD).
  
  
  RESULTS
  The assay had 97% specificity and 83% sensitivity for detecting iCTCs in blood of EOC patients. iCTCs were detected in each monitoring patient (31/31, 100%) and in 110 of the 129 blood samples (85.3%). The concordance between changes in iCTCs/CA125 levels and changes in the intervals associated with no evidence of disease (NED) were markedly stronger (specificity: CA125 93.8%; iCTCs 90.6%), whereas increases in iCTCs (79.5%) were more sensitive than increases in CA125 (67.6%) to predict PD or relapse. Among the six patients who had greater than 6 measurements, iCTCs but not CA125 antedated changes in clinical status from PD to NED during and after chemotherapy and predated relapse.
  
  
  CONCLUSIONS
  Serial measurements of iCTCs could predict therapeutic responsiveness in 31 EOC patients who underwent standard taxol/carboplatin therapy.
authors.affiliation: Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Pearl
authors.affiliation: Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA.
authors.forename: Huan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA.
authors.forename: Shaun
authors.initials: S
authors.lastname: Tulley
authors.affiliation: Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Stony Brook Medicine, Stony Brook, NY 11794, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Golightly
authors.affiliation: Department of Medicine, Stony Brook Medicine, Stony Brook, NY 11794, USA; Department of Medicine and Research, Veterans Affairs Medical Center, Northport, NY 11768, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Zucker
authors.affiliation: Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA. Electronic address: wentien@vitatex.com.
authors.forename: Wen-Tien
authors.initials: WT
authors.lastname: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D015331:Cohort Studies; D004784:Environmental Monitoring / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000097:blood; D008565:Membrane Proteins / Q000097:blood; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000473:pathology; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D012697:Serine Endopeptidases / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C451759:MUC16 protein, human; D008565:Membrane Proteins; D012697:Serine Endopeptidases; C478147:seprase, human
keywords: CTC; Cell invasion; Circulating cancer cells; Metastasis detection; Ovarian cancer; Treatment monitoring