title: Vimentin and Ki67 expression in circulating tumour cells derived from castrate-resistant prostate cancer.
abstract: BACKGROUND
  High circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently CTC number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer (mCRPC). Ki67 and vimentin are well-characterised markers of tumour cell proliferation and the epithelial-mesenchymal transition (EMT), respectively. Here we asked if the expression of vimentin and Ki67 in CTCs offered prognostic or predictive information in mCRPC.
  
  
  METHODS
  In two separate patient cohorts, anti-vimentin or anti-Ki67 antibodies were added to the free channel in the CellSearch® system for analysis of peripheral blood samples. For each cohort, association of CTC number with clinical characteristics were assessed using Fisher's exact, Mann-Whitney and chi-squared tests. Kaplan-Meier method and log-rank tests were used to analyse overall survival (OS) of vimentin-expressing and Ki67-expressing CTC patient cohorts.
  
  
  RESULTS
  In this retrospective analysis, CTC vimentin expression was analysed in 142 blood samples from 93 patients, and CTC Ki67 expression was analysed in 90 blood samples from 51 patients. In the vimentin cohort, 80/93 (86 %) of baseline samples from patients were CTC-positive overall (≥1 total CTC per 7.5 mls blood), and 30/93 (32.3 %) vimentin CTC-positive (≥1 vimentin-positive CTC per 7.5 mls blood). 41/51 (80.4 %) of baseline samples from patients in the Ki67 cohort were CTC-positive overall, and 23/51 (45.1 %) Ki67 CTC-positive (≥1 Ki67-positive CTC per 7.5 mls blood). There was no significant difference in baseline PSA in patients with vimentin-positive CTC at baseline versus those with no vimentin-positive CTC at baseline (p = 0.33). A significant reduction in OS was shown in patients with vimentin-positive CTC compared to those without vimentin-positive CTC (median 305 days vs 453 days, p = 0.0293). There was no significant difference in baseline PSA in patients with Ki67-positive CTC at baseline versus those without Ki67-positive CTC (p = 0.228), but OS was significantly reduced in the Ki67-positive CTC group (median 512 days vs 751 days, p = 0.0091). No changes in relative proportion of vimentin- or Ki67-positive CTCs were observed in post-treatment samples compared to baseline.
  
  
  CONCLUSIONS
  Analysis of vimentin and Ki67 expression can straightforwardly be assessed in CTCs from patients with mCRPC. Poorer survival outcomes were observed in vimentin- and Ki67-positive CTC patients.
  CEC-CTC (IDRCB2008-AOO585-50) and Petrus ( NCT01786031 ).
authors.affiliation: INSERM U981, University of Paris-Sud XI, Translational Research Laboratory, Gustave Roussy Cancer Campus, Villejuif, France. colin.lindsay@gustaveroussy.fr.
authors.forename: C R
authors.initials: CR
authors.lastname: Lindsay
authors.affiliation: Department of Medical Oncology, Bergonie Cancer Institute, Bordeaux, France. sylvestre.lemoulec@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Le Moulec
authors.affiliation: INSERM U981, University of Paris-Sud XI, Translational Research Laboratory, Gustave Roussy Cancer Campus, Villejuif, France. fanny.billiot@gustaveroussy.fr.
authors.forename: F
authors.initials: F
authors.lastname: Billiot
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. yohann.loriot@gustaveroussy.fr.
authors.forename: Y
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. maud.ngocamus@gustaveroussy.fr.
authors.forename: M
authors.initials: M
authors.lastname: Ngo-Camus
authors.affiliation: INSERM U981, University of Paris-Sud XI, Translational Research Laboratory, Gustave Roussy Cancer Campus, Villejuif, France. philippe.vielh@gustaveroussy.fr.|Department of Biopathology, Gustave Roussy Cancer Campus, Villejuif, France. philippe.vielh@gustaveroussy.fr.
authors.forename: P
authors.initials: P
authors.lastname: Vielh
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. karim.fizazi@gustaveroussy.fr.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. christophe.massard@gustaveroussy.fr.
authors.forename: C
authors.initials: C
authors.lastname: Massard
authors.affiliation: INSERM U981, University of Paris-Sud XI, Translational Research Laboratory, Gustave Roussy Cancer Campus, Villejuif, France. francoise.farace@gustaveroussy.fr.
authors.forename: F
authors.initials: F
authors.lastname: Farace
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D003131:Combined Modality Therapy; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D015203:Reproducibility of Results; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D014746:Vimentin