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 Journal Article


Authors: Helo, P.; Cronin, A. M.; Danila, D. C.; Wenske, S.; Gonzalez-Espinoza, R.; Anand, A.; Koscuiszka, M.; Väänänen, R. M.; Pettersson, K.; Chun, F. K. H.; Steuber, T.; Huland, H.; Guillonneau, B. D.; Eastham, J. A.; Scardino, P. T.; Fleisher, M.; Scher, H. I.; Lilja, H.
Article 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: 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 (≥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 τ, 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.PSCAmRNA was detectedinonly 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. © 2009 American Association for Clinical Chemistry.
Keywords: adult; cancer survival; controlled study; human tissue; bone neoplasms; bone tumor; survival rate; unclassified drug; human cell; major clinical study; case control study; genetics; case-control studies; cancer localization; bone metastasis; methodology; antineoplastic agent; prostate specific antigen; metabolism; metastasis; reverse transcription polymerase chain reaction; pathology; cell assay; prostate cancer; prostatic neoplasms; soft tissue; blood; messenger rna; blood sampling; neoplastic cells, circulating; reverse transcriptase polymerase chain reaction; rna, messenger; quantitative analysis; prostate tumor; immunomagnetic separation; tumor cell; kallikrein; real time polymerase chain reaction; castration; orchiectomy; kallikrein related peptidase 2; kallikrein related peptidase 3; prostate stem cell antigen; volunteer; tumor embolism; kallikreins
Journal Title: Clinical Chemistry
Volume: 55
Issue: 4
ISSN: 0009-9147
Publisher: American Association for Clinical Chemistry  
Date Published: 2009-04-01
Start Page: 765
End Page: 773
Language: English
DOI: 10.1373/clinchem.2008.117952
PUBMED: 19233911
PROVIDER: scopus
PMCID: PMC2782624
DOI/URL:
Notes: --- - "Cited By (since 1996): 8" - "Export Date: 30 November 2010" - "CODEN: CLCHA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Peter T Scardino
    621 Scardino
  2. Pauliina Helo
    3 Helo
  3. Sven Wenske
    5 Wenske
  4. Hans Gosta Lilja
    286 Lilja
  5. Angel M Cronin
    145 Cronin
  6. James Eastham
    427 Eastham
  7. Martin Fleisher
    242 Fleisher
  8. Howard Scher
    835 Scher
  9. Daniel C Danila
    83 Danila
  10. Aseem Anand
    45 Anand