TMPRSS2

ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia

Kyung Park, James T. Dalton, Ramesh Narayanan, Christopher E. Barbieri, Michael L. Hancock, David G. Bostwick, Mitchell S. Steiner, Mark A. Rubin

Research output: Contribution to journalArticle

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Abstract

Purpose: High-grade prostatic intraepithelial neoplasia (HGPIN) is considered a precursor lesion of prostate cancer (PCa). The predictive value of ERG gene fusion in HGPIN for PCa was interrogated as a post hoc analysis in the context of a randomized clinical trial. Patients and Methods: The GTx Protocol G300104 randomly assigned 1,590 men with biopsy-diagnosed HGPIN to receive toremifene or placebo for 3 years or until a diagnosis of PCa was made on prostate biopsy. As part of this phase III clinical trial, a central pathologist evaluated biopsies of patients with isolated HGPIN at baseline and 12, 24, and 36 months of follow-up. ERG immunohistochemistry was performed on biopsies from 461 patients and evaluated for protein overexpression. Results: ERG expression was detected in 11.1% of patients (51 of 461 patients) with isolated HGPIN. In the first year and during the 3-year clinical trial, 14.7% and 36.9% of 461 patients were diagnosed with PCa, respectively. Patients with ERG expression were more likely to develop PCa, with 27 (53%) of 51 ERG-positive and 143 (35%) of 410 ERG-negative patients experiencing progression to PCa (P = .014, Fisher's exact test). ERG expression was not associated with age, baseline PSA, Gleason score, or tumor volume. Conclusion: This study underscores the necessity of more stringent follow-up for men with HGPIN that is also positive for ERG overexpression. Clinicians should consider molecular characterization of HGPIN as a means to improve risk stratification.

Original languageEnglish (US)
Pages (from-to)206-211
Number of pages6
JournalJournal of Clinical Oncology
Volume32
Issue number3
DOIs
StatePublished - Jan 20 2014

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Prostatic Intraepithelial Neoplasia
Gene Fusion
Prostatic Neoplasms
Biopsy
Toremifene
Phase III Clinical Trials
Neoplasm Grading
Tumor Burden
Prostate
Randomized Controlled Trials
Immunohistochemistry
Placebos
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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TMPRSS2 : ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia. / Park, Kyung; Dalton, James T.; Narayanan, Ramesh; Barbieri, Christopher E.; Hancock, Michael L.; Bostwick, David G.; Steiner, Mitchell S.; Rubin, Mark A.

In: Journal of Clinical Oncology, Vol. 32, No. 3, 20.01.2014, p. 206-211.

Research output: Contribution to journalArticle

Park, Kyung ; Dalton, James T. ; Narayanan, Ramesh ; Barbieri, Christopher E. ; Hancock, Michael L. ; Bostwick, David G. ; Steiner, Mitchell S. ; Rubin, Mark A. / TMPRSS2 : ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 3. pp. 206-211.
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abstract = "Purpose: High-grade prostatic intraepithelial neoplasia (HGPIN) is considered a precursor lesion of prostate cancer (PCa). The predictive value of ERG gene fusion in HGPIN for PCa was interrogated as a post hoc analysis in the context of a randomized clinical trial. Patients and Methods: The GTx Protocol G300104 randomly assigned 1,590 men with biopsy-diagnosed HGPIN to receive toremifene or placebo for 3 years or until a diagnosis of PCa was made on prostate biopsy. As part of this phase III clinical trial, a central pathologist evaluated biopsies of patients with isolated HGPIN at baseline and 12, 24, and 36 months of follow-up. ERG immunohistochemistry was performed on biopsies from 461 patients and evaluated for protein overexpression. Results: ERG expression was detected in 11.1{\%} of patients (51 of 461 patients) with isolated HGPIN. In the first year and during the 3-year clinical trial, 14.7{\%} and 36.9{\%} of 461 patients were diagnosed with PCa, respectively. Patients with ERG expression were more likely to develop PCa, with 27 (53{\%}) of 51 ERG-positive and 143 (35{\%}) of 410 ERG-negative patients experiencing progression to PCa (P = .014, Fisher's exact test). ERG expression was not associated with age, baseline PSA, Gleason score, or tumor volume. Conclusion: This study underscores the necessity of more stringent follow-up for men with HGPIN that is also positive for ERG overexpression. Clinicians should consider molecular characterization of HGPIN as a means to improve risk stratification.",
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