TMPRSS2:ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia.

TitleTMPRSS2:ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia.
Publication TypeJournal Article
Year of Publication2014
AuthorsPark K, Dalton JT, Narayanan R, Barbieri CE, Hancock ML, Bostwick DG, Steiner MS, Rubin MA
JournalJ Clin Oncol
Volume32
Issue3
Pagination206-11
Date Published2014 Jan 20
ISSN1527-7755
KeywordsAged, Antineoplastic Agents, Hormonal, Biopsy, Disease Progression, Gene Expression Regulation, Neoplastic, Gene Fusion, Humans, Male, Middle Aged, Neoplasm Grading, Oncogene Proteins, Fusion, Prostatic Intraepithelial Neoplasia, Prostatic Neoplasms, Toremifene, Tumor Markers, Biological, Up-Regulation
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.

DOI10.1200/JCO.2013.49.8386
Alternate JournalJ. Clin. Oncol.
PubMed ID24297949
PubMed Central IDPMC3887478
Grant ListR01 CA152057 / CA / NCI NIH HHS / United States
U01 CA111275 / CA / NCI NIH HHS / United States
U01 CA111275 / CA / NCI NIH HHS / United States