title: Pooled analysis of the prognostic relevance of disseminated tumor cells in the bone marrow of patients with ovarian cancer.
abstract: OBJECTIVE
  Detection of disseminated tumor cells (DTCs) in the bone marrow (BM) of patients with breast cancer is associated with poor outcomes. Recent studies demonstrated that DTCs may serve as a prognostic factor in ovarian cancer. The aim of this 3-center study was to evaluate the impact of BM status on survival in a large cohort of patients with ovarian cancer.
  
  
  METHODS
  Four hundred ninety-five patients with primary ovarian cancer were included in this 3-center prospective study. Bone marrow aspirates were collected intraoperatively from the iliac crest. Disseminated tumor cells were identified by antibody staining and by cytomorphology. Clinical outcome was correlated with the presence of DTCs.
  
  
  RESULTS
  Disseminated tumor cells were detected in 27% of all BM aspirates. The number of cytokeratin-positive cells ranged from 1 to 42 per 2 × 10⁶ mononuclear cells. Disseminated tumor cell status did correlate with histologic subtype but not with any of the other established clinicopathologic factors. The overall survival was significantly shorter among DTC-positive patients compared to DTC-negative patients (51 months; 95% confidence interval, 37-65 months vs 33 months; 95% confidence interval, 23-43 months; P = 0.023). In the multivariate analysis, BM status, International Federation of Gynecology and Obstetrics stage, nodal status, resection status, and age were independent predictors of reduced overall survival, whereas only BM status, International Federation of Gynecology and Obstetrics stage, and resection status independently predicted progression-free survival.
  
  
  CONCLUSIONS
  Tumor cell dissemination into the BM is a common phenomenon in ovarian cancer. Disseminated tumor cell detection has the potential to become an important biomarker for prognostication and disease monitoring in patients with ovarian cancer.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Düsseldorf, University of Düsseldorf, Germany. tanja.fehm@med.uni-tuebingen.de
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Banys
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.forename: Christina
authors.initials: C
authors.lastname: Blassl
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartkopf
authors.forename: Claes
authors.initials: C
authors.lastname: Trope
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.forename: Natalia
authors.initials: N
authors.lastname: Krawczyk
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.forename: Sabine
authors.initials: S
authors.lastname: Kasimir-Bauer
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000401:mortality* / Q000556:secondary / Q000601:surgery; D002288:Adenocarcinoma, Mucinous / Q000401:mortality* / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019046:Bone Marrow Neoplasms / Q000401:mortality* / Q000556:secondary / Q000601:surgery; D018284:Cystadenocarcinoma, Serous / Q000401:mortality* / Q000556:secondary / Q000601:surgery; D016889:Endometrial Neoplasms / Q000401:mortality* / Q000556:secondary / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult