title: Circulating prostate tumor cells detected by reverse transcription-PCR in men with localized or castration-refractory prostate cancer: concordance with CellSearch assay and association with bone metastases and with survival.
abstract: BACKGROUND
  Reverse transcription-PCR (RT-PCR) assays have been used for analysis of circulating tumor cells (CTCs), but their clinical value has yet to be established. We assessed men with localized prostate cancer or castration-refractory prostate cancer (CRPC) for CTCs via real-time RT-PCR assays for KLK3 [kallikrein-related peptidase 3; i.e., prostate-specific antigen (PSA)] and KLK2 mRNAs. We also assessed the association of CTCs with disease characteristics and survival.
  
  
  METHODS
  KLK3, KLK2, and PSCA (prostate stem cell antigen) mRNAs were measured by standardized, quantitative real-time RT-PCR assays in blood samples from 180 localized-disease patients, 76 metastatic CRPC patients, and 19 healthy volunteers. CRPC samples were also tested for CTCs by an immunomagnetic separation system (CellSearch; Veridex) approved for clinical use.
  
  
  RESULTS
  All healthy volunteers were negative for KLK mRNAs. Results of tests for KLK3 or KLK2 mRNAs were positive (> or =80 mRNAs/mL blood) in 37 patients (49%) with CRPC but in only 15 patients (8%) with localized cancer. RT-PCR and CellSearch CTC results were strongly concordant (80%-85%) and correlated (Kendall tau, 0.60-0.68). Among CRPC patients, KLK mRNAs and CellSearch CTCs were closely associated with clinical evidence of bone metastases and with survival but were only modestly correlated with serum PSA concentrations. PSCA mRNA was detected in only 7 CRPC patients (10%) and was associated with a positive KLK mRNA status.
  
  
  CONCLUSIONS
  Real-time RT-PCR assays of KLK mRNAs are highly concordant with CellSearch CTC results in patients with CRPC. KLK2/3-expressing CTCs are common in men with CRPC and bone metastases but are rare in patients with metastases diagnosed only in soft tissues and patients with localized cancer.
authors.affiliation: Departments of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center,New York, NY 10065, USA.
authors.forename: Pauliina
authors.initials: P
authors.lastname: Helo
authors.forename: Angel M
authors.initials: AM
authors.lastname: Cronin
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Danila
authors.forename: Sven
authors.initials: S
authors.lastname: Wenske
authors.forename: Rita
authors.initials: R
authors.lastname: Gonzalez-Espinoza
authors.forename: Aseem
authors.initials: A
authors.lastname: Anand
authors.forename: Michael
authors.initials: M
authors.lastname: Koscuiszka
authors.forename: Riina-Minna
authors.initials: RM
authors.lastname: Väänänen
authors.forename: Kim
authors.initials: K
authors.lastname: Pettersson
authors.forename: Felix K-H
authors.initials: FK
authors.lastname: Chun
authors.forename: Thomas
authors.initials: T
authors.lastname: Steuber
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.forename: Bertrand D
authors.initials: BD
authors.lastname: Guillonneau
authors.forename: James A
authors.initials: JA
authors.lastname: Eastham
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: Martin
authors.initials: M
authors.lastname: Fleisher
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D008297:Male; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D015996:Survival Rate
chemical_list: D012333:RNA, Messenger; D007610:Kallikreins