title: Prognostic analysis of invasive circulating tumor cells (iCTCs) in epithelial ovarian cancer.
abstract: OBJECTIVE
  Circulating tumor cells (CTCs) have been introduced as a biomarker in detecting advanced epithelial ovarian cancer (EOC). The goals are to examine the prevalence of the invasive subpopulation of CTCs (iCTCs) in patients at high risk of EOC and to compare this biomarker to serum CA125.
  
  
  METHODS
  We used a unique cell adhesion matrix (CAM)-based, functional cell enrichment and identification platform to isolate iCTCs from 129 preoperative patients. We confirmed the identity of iCTCs using positive epithelial (Epi+) markers and negative hematopoietic lineage (HL-) markers. Sensitivity and specificity of the assays were examined and iCTCs/CA125 were correlated with overall survival (OS), progression-free survival (PFS) and clinical parameters.
  
  
  RESULTS
  We found a 41.2% sensitivity, 95.1% specificity and 77.8% positive predictive value (PPV) of the iCTC assay in detecting patients with stage I and II EOC malignancy, and a 83% sensitivity and 97.3% PPV in detecting all stages of EOC malignancy. However, a positive CA125 test provided weak evidence to detect stage I and II malignancy (61.6% PPV) and all EOC (92.1% PPV), because of its 76.2% specificity. A significantly stronger concordance in OS and PFS of clinical factors (tumor stage, debulking and platinum sensitivity) was noted for elevated iCTCs than for serum CA125.
  
  
  CONCLUSIONS
  The CAM-initiated CTC enrichment/identification method enabled the detection of early stage EOC. iCTCs were better correlated with worse OS and PFS, more specific and better PPV than CA125 in detecting EOC malignancy in patients at high risk of EOC.
authors: Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA.
authors: Michael L
authors: ML
authors: Pearl
authors: Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA.
authors: Qiang
authors: Q
authors: Zhao
authors: Department of Preventive Medicine, Stony Brook Medicine, Stony Brook, NY 11794, USA; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
authors: Jie
authors: J
authors: Yang
authors: Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA.
authors: Huan
authors: H
authors: Dong
authors: Division of Gynecologic Oncology, Stony Brook Medicine, Stony Brook, NY 11794, USA; Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA.
authors: Shaun
authors: S
authors: Tulley
authors: Department of Preventive Medicine, Stony Brook Medicine, Stony Brook, NY 11794, USA; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
authors: Qiao
authors: Q
authors: Zhang
authors: Department of Pathology, Stony Brook Medicine, Stony Brook, NY 11794, USA.
authors: Marc
authors: M
authors: Golightly
authors: 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: Stanley
authors: S
authors: Zucker
authors: 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: Wen-Tien
authors: WT
authors: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D002452:Cell Count; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen
keywords: CTC; Cell invasion; Metastasis detection; Ovarian cancer