title: ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer.
abstract: BACKGROUND
  We recently showed that the presence of ERCC1+CTCs is an independent predictive biomarker for platinum-resistance and poor prognosis of ovarian cancer. The goal of our current research was to determine how the auxiliary assessment of ERCC1-transcripts influences overall CTC-detection rate. We extended this investigation from an initially predictive setting to paired pre- and post-therapeutic blood analysis in order to see, whether ERCC1+CTCs dynamics mirror response to chemotherapy.
  
  
  METHODS
  65 Paired blood samples (10ml) of primary ovarian cancer patients at primary diagnosis and after chemotherapy were studied for CTCs with the AdnaTest Ovarian Cancer (QIAGEN Hannover GmbH). We analyzed the tumor-associated transcripts EpCAM, MUC-1 and CA-125. ERCC1-transcripts were investigated in a separate approach by singleplex RT-PCR.
  
  
  RESULTS
  Auxiliary assessment of ERCC1-transcripts enhanced the overall CTC-detection rate up to 17%. ERCC1+CTCs (defined as positive for one of the AdnaTest markers plus ERCC1-positivity) were detected in 15% of patients at primary diagnosis and in 12% after chemotherapy. The presence of ERCC1+CTCs after chemotherapy correlated with platinum-resistance (P=0.01), reduced PFS (P=0.0293) and OS (P=0.0008) and their persistence indicated poor post-therapeutic outcome (PFS: P=0.005; OS: P=0.0058). Interestingly, the assessment of ERCC1-transcripts alone was sufficient for the detection of prognostic relevant ERCC1-expressing CTCs.
  
  
  CONCLUSIONS
  Auxiliary assessment of ERCC1-transcripts expands the phenotypic spectrum of CTC detection and defines an additional overlapping fraction of ERCC1-expressing CTCs, which are potentially selected by platinum-based chemotherapy. Specifically, we suggest that ERCC1+CTCs could additionally be useful as a surrogate for monitoring platinum-based chemotherapy and to assess the post-therapeutic outcome of ovarian cancer.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.|German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Issam
authors.initials: I
authors.lastname: Chebouti
authors.affiliation: Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.|German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jan Dominik
authors.initials: JD
authors.lastname: Kuhlmann
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.|German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Buderath
authors.affiliation: ACOMED Statistik, Department of Biostatics, Magdeburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Weber
authors.affiliation: Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.|German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.affiliation: QIAGEN Hannover GmbH, Langenhagen, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Bokeloh
authors.affiliation: QIAGEN Hannover GmbH, Langenhagen, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Hauch
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.|German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.|German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kasimir-Bauer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D004720:Endonucleases / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: ERCC1; circulating tumor cells; ovarian cancer; platinum-resistance; prognosis