TMPRSS2-ERG Status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate Journal Article

Authors: Danila, D. C.; Anand, A.; Sung, C. C.; Heller, G.; Leversha, M. A.; Cao, L.; Lilja, H.; Molina, A.; Sawyers, C. L.; Fleisher, M.; Scher, H. I.
Article Title: TMPRSS2-ERG Status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate
Abstract: Background: Abiraterone acetate (AA) is an androgen biosynthesis inhibitor shown to prolong life in patients with castration-resistant prostate cancer (CRPC) already treated with chemotherapy. AA treatment results in dramatic declines in prostate-specific antigen (PSA) in some patients and no declines in others, suggesting the presence of molecular determinants of sensitivity in tumors. Objective: To study the role of transmembrane protease, serine 2 (TMPRSS2)-v-ets erythroblastosis virus E26 oncogene homolog (ERG) fusion, an androgen-dependent growth factor, in circulating tumor cells (CTCs) as a biomarker of sensitivity to AA. Design, setting, and participants: The predictive value of TMPRSS2-ERG status was studied in 41 of 48 men with postchemotherapy-treated CRPC enrolled in sequential phase 2 AA trials. Intervention: Patients received AA 1000 mg daily and continuously. Measurements: TMPRSS2-ERG status was characterized by a sensitive, analytically valid reverse transcription polymerase chain reaction assay in CTCs enriched from ethylene-diaminetetraacetic acid anticoagulated blood obtained prior to AA treatment. Outcomes were measured by PSA Working Group 1 criteria. Results and limitations: Standard procedures for specimen acquisition, processing, and testing using the validated TMPRSS2-ERG assay on a multiplex platform gave intra-assay and interassay coefficients of variation <7%. TMPRSS2-ERG fusion was present in 15 of 41 patients (37%), who had a median baseline CTC count of 17 (interquartile range: 7-103 cells per 7.5 ml). A PSA decline ≥50% was observed in 7 of 15 patients (47%) with the fusion and in 10 of 26 patients (38%) without the fusion. Although limited by the low number of patients, a posttherapy CTC count of less than five per 7.5 ml was prognostic for longer survival relative to a CTC count five or more. TMPRSS2-ERG status did not predict a decline in PSA or other clinical outcomes. Conclusions: Molecular profiles of CTCs with an analytically valid assay identified the presence of the prostate cancer-specific TMPRSS2-ERG fusion but did not predict for response to AA treatment. This finding demonstrates the role of CTCs as surrogate tissue that can be obtained in a routine practice setting. Trial registration: NCT00474383 (COU-AA-003), NCT00485303 (COU-AA-004). © 2011 European Association of Urology.
Keywords: adult; clinical article; treatment outcome; aged; survival rate; unclassified drug; prednisone; patient selection; chemotherapy, adjuvant; radiotherapy, adjuvant; outcome assessment; prostate specific antigen; reproducibility of results; in situ hybridization, fluorescence; reverse transcription polymerase chain reaction; tumor markers, biological; time factors; prostate cancer; prostate-specific antigen; prostatic neoplasms; fluorescence in situ hybridization; neoplastic cells, circulating; reverse transcriptase polymerase chain reaction; enzyme inhibitors; prostatectomy; biomarker; oncogene proteins, fusion; predictive value of tests; new york city; proteinase; abiraterone acetate; orchiectomy; antineoplastic agents, hormonal; drug sensitivity; circulating tumor cells; predictive value; genetic markers; circulating tumor cell; castration resistant prostate cancer; abiraterone; kaplan-meier estimate; virus oncogene; tmprss2-erg fusion; edetic acid; steroid 17-alpha-hydroxylase; androstadienes; transmembrane protease serine 2; erythroblastosis virus e26 oncogene homolog
Journal Title: European Urology
Volume: 60
Issue: 5
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2011-11-01
Start Page: 897
End Page: 904
Language: English
DOI: 10.1016/j.eururo.2011.07.011
PROVIDER: scopus
PMCID: PMC3185163
PUBMED: 21802835
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 2 November 2011" - "CODEN: EUURA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Charles L Sawyers
    153 Sawyers
  2. Glenn Heller
    291 Heller
  3. Hans Gosta Lilja
    286 Lilja
  4. Martin Fleisher
    236 Fleisher
  5. Howard Scher
    816 Scher
  6. Daniel C Danila
    82 Danila
  7. Aseem Anand
    45 Anand
  8. Clifford Sung
    7 Sung
  9. Long Cao
    8 Cao