title: Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence.
abstract: OBJECTIVE
  To determine the utility of novel combinations of biomarkers, using both a one-step and two-step assay format, to distinguish serum of early ovarian cancer patients from that of healthy controls and to discern the utility of these biomarkers in a monitoring capacity.
  
  
  METHODS
  For ovarian cancer detection, HE4, Glycodelin, MMP7, SLPI, Plau-R, MUC1, Inhibin A, PAI-1, and CA125 were evaluated in a cohort of 200 women with ovarian cancer and 396 healthy age-matched controls. Each biomarker was assessed by serum-based immunoassays utilizing novel monoclonal antibody pairs or commercial kits. For detection of disease recurrence, HE4, Glycodelin, MMP7 and CA125 were evaluated in 260 samples from 30 patients with OC monitored longitudinally after diagnosis.
  
  
  RESULTS
  Based upon ROC curve analysis, the sensitivity/specificity of specific biomarker combination algorithms ranged from 59.0%/99.7% to 80.5%/96.5% for detection of early stage ovarian cancer and 76.9%/99.7% to 89.2%/97.2% for detection of late stage cancer. In monitoring evaluation of 27 patients who experienced recurrence of OC, sensitivity for predicting recurrence was 100% for the biomarker panel and 96% for CA125. At least one of the panel biomarkers was elevated earlier (range 6-69 weeks) than CA125 and prior to clinical evidence of recurrence in 14/27 (52%) patients.
  
  
  CONCLUSIONS
  We have developed and demonstrated the utility of several one- and two-step multi-marker combinations with acceptable test characteristics for possible use in an ovarian cancer screening population. A subset of this panel may also provide adjunctive information to rising CA125 levels in disease monitoring.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710, USA. havri001@mc.duke.edu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Havrilesky
authors.forename: Clark M
authors.initials: CM
authors.lastname: Whitehead
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Rubatt
authors.forename: Robert L
authors.initials: RL
authors.lastname: Cheek
authors.forename: John
authors.initials: J
authors.lastname: Groelke
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Malinowski
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Fischer
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor