title: Detection of circulating tumor cells in patients with localized and metastatic prostatic carcinoma: clinical implications.
abstract: OBJECTIVE
  To determine the frequency with which prostate-specific antigen (PSA)-positive cells can be detected in the peripheral blood of patients with prostatic cancer in different stages and with different sensitivities to hormonal therapy.
  
  
  METHODS
  Peripheral blood from 107 men with prostatic cancer and 27 non-prostate cancer controls was analyzed for PSA mRNA using reverse-transcriptase polymerase chain reaction (RT-PCR) and Southern blotting.
  
  
  RESULTS
  The lower limit of detection was one PSA-producing cell diluted into 1 x 10(6) blood mononuclear cells. The test detected PSA mRNA in four of 25 patients (16%) with clinically organ-confined (T1-2) disease, three of 10 (30%) with T3-4 or N+ tumors, and 25 of 72 (35%) with distant metastases. None of the control samples were positive. An increase in positivity was observed with increasing PSA levels. Within the subgroup of patients with distant metastases, positivity was observed in six of 16 patients (38%) with normal or undetectable PSA levels after hormonal therapy and, overall, in 37% of patients (21 of 57) with androgen-independent disease.
  
  
  CONCLUSIONS
  An RT-PCR-based assay for PSA mRNA can detect circulating cells in the peripheral blood of patients with prostatic cancer. The frequency of positivity increases with tumor stage. A unique observation was the detection of cells in patients with no measurable PSA on hormonal therapy. This suggests that continued seeding of distant sites may still be occurring in these patients, despite seemingly successful therapy. The relationship between continued seeding, disease progression, and survival will require further study.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Ghossein
authors.forename: H I
authors.initials: HI
authors.lastname: Scher
authors.forename: W L
authors.initials: WL
authors.lastname: Gerald
authors.forename: W K
authors.initials: WK
authors.lastname: Kelly
authors.forename: T
authors.initials: T
authors.lastname: Curley
authors.forename: A
authors.initials: A
authors.lastname: Amsterdam
authors.forename: Z F
authors.initials: ZF
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Rosai
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D005069:Evaluation Studies as Topic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000097:blood* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012680:Sensitivity and Specificity
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017430:Prostate-Specific Antigen