title: Significance of apoptotic and non-apoptotic disseminated tumor cells in the bone marrow of patients with clinically localized prostate cancer.
abstract: BACKGROUND
  Disseminated tumor cells (DTC) can be detected in a high proportion of patients with localized solid malignancies. In prostate cancer (PC), determination of DTCs is critically discussed as there are conflicting results on their prognostic value. The aim of the present study was to evaluate the presence and prognostic role of DTCs in PC patients with a high risk of disease recurrence.
  
  
  METHODS
  248 patients with clinically localized PC undergoing radical prostatectomy with features of increased risk of recurrence (PSA ≥10 ng/ml or Gleason score ≥ 4 + 3 = 7 or pT ≥3) were included. All patients underwent intraoperative bone marrow (BM) aspiration biopsy. BM cells were evaluated by immunocytochemistry for cytokeratines and the apoptosis marker caspase-cleaved cytokeratin 18 (M30). Results of immunocytochemistry were correlated with clinical and pathological parameters and clinical outcome of the patients.
  
  
  RESULTS
  Of 248 patients, 47 (19.0%) had evidence of DTCs at time of radical prostatectomy. In 17 of these 47 patients (36.2%), DTCs expressed the apoptosis marker M30. We observed no correlation between the presence of DTCs and tumor stage, nodal stage, prostate-specific antigen, or Gleason score. After a median-follow-up of 58 months (23-76), no differences in rates of biochemical recurrence, development of metastases and cancer-specific death were observed between patients with and without DTCs while apoptosis markers had no role.
  
  
  CONCLUSIONS
  In a single-centre cohort of patients with increased risk for disease recurrence, the presence of DTCs at the time of prostatectomy does not influence clinical outcome. For the first time in patients with PC, DTCs were evaluated for immunocytological features indicating apoptosis. Due to conflicting results of studies on DTCs, BM biopsies at time of radical prostatectomy cannot be recommended as a standard procedure in patients with clinically localized PC.
authors.affiliation: Department of Urology, University Hospital, Tübingen, Germany; Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Tilman
authors.initials: T
authors.lastname: Todenhöfer
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Frank
authors.initials: F
authors.lastname: Faber
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.forename: David
authors.initials: D
authors.lastname: Schilling
authors.forename: Ursula
authors.initials: U
authors.lastname: Kühs
authors.forename: Stefan
authors.initials: S
authors.lastname: Aufderklamm
authors.forename: Simone
authors.initials: S
authors.lastname: Bier
authors.forename: Johannes
authors.initials: J
authors.lastname: Mischinger
authors.forename: Georgios
authors.initials: G
authors.lastname: Gakis
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Christian
authors.initials: C
authors.lastname: Schwentner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology*; D006801:Humans; D053538:Keratin-18 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery
chemical_list: D053538:Keratin-18; C561463:M30 cytokeratin-18 peptide, human; D010446:Peptide Fragments
keywords: bone marrow; metastases; micrometastases; minimal residual disease; prostate cancer; risk factors