title: Analysis of disseminated tumor cells before and after platinum based chemotherapy in primary ovarian cancer. Do stem cell like cells predict prognosis?
abstract: BACKGROUND
  We recently reported that the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) of primary ovarian cancer patients (POC pts) correlated with reduced progression free survival (PFS) and overall survival (OS). Here we analyzed whether the negative prognostic influence was related to DTC persistence after platinum based chemotherapy and/or due to DTCs associated with stem cell character.
  
  
  RESULTS
  DTCs were detected in 33/79 pts (42%) before and in 32/79 pts (41%) AT. Persistent DTCs were found in 13 pts, 20 pts were only positive BT, 19 pts AT and 27 pts had no DTCs. Whereas the presence of DTCs BT significantly correlated with reduced OS (p = 0.02), pts initially DTCneg BT but DTCpos AT had a significantly shorter PFS (p = 0.03). DTC persistence resulted in a shorter PFS and OS reaching borderline significance (p = 0.06; p = 0.07). LIN-28-and SOX-2 positive cells were detected in all eight pts AT.
  
  
  METHODS
  79 POC pts were studied for DTCs before therapy (BT) and after therapy (AT) using immunocytochemistry. Eight pts harboring at least five DTCs AT were further analyzed on two additional slides by four-fold immunofluorescence staining for DAPI, Cytokeratin (CK), SOX-2 or LIN-28, CD45 and CD34 (Cy5). A stem-like tumor cell was classified as Dapipos, CD45neg, CD34neg, SOX-2pos/LIN-28pos and CKpos or CKneg.
  
  
  CONCLUSIONS
  Stem cell associated proteins are expressed in DTCs that are present AT and their presence seem to be correlated with a worse outcome. Additional therapeutic regimens may be necessary to eliminate these cells.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.
authors.forename: Issam
authors.initials: I
authors.lastname: Chebouti
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Blassl
authors.affiliation: Department of Gynecology and Obstetrics, Carl-Gustav-Carus University, TU Dresden, Dresden, Germany.
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Neubauer
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kasimir-Bauer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology*; D001859:Bone Neoplasms / Q000556:secondary; D016190:Carboplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000401:mortality / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D017239:Paclitaxel / Q000627:therapeutic use; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D017239:Paclitaxel
keywords: bone marrow; disseminated tumor cells; primary ovarian cancer; stem cells