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Characterization of TMPRSS2-ERG Fusion High-Grade Prostatic Intraepithelial Neoplasia and Potential Clinical Implications

Authors' Affiliations: ¹ Department of Pathology, Brigham and Women's Hospital; ² Harvard Medical School; ³ Departments of Pathology and Urology, Beth Israel Deaconess Medical Center; ⁴ Dana-Farber Harvard Comprehensive Cancer Center, Boston, Massachusetts; ⁵ Department of Pathology, University of Ulm, Ulm, Germany; ⁶ Comprehensive Cancer Center, University of California, San Francisco, California; ⁷ Departments of Pathology and Oncology, McGill University Faculty of Medicine, Montreal, Quebec, Canada; ⁸ Department of Pathology and Scott Department of Urology, Baylor College of Medicine, Houston, Texas; ⁹ Departments of Pathology and Urology, University of Michigan, Ann Arbor, Michigan; and ¹⁰ Broad Institute of Massachusetts Institute of Technology and Harvard Medical School, Cambridge, Massachusetts

Requests for reprints: Mark A. Rubin, Department of Pathology, C-410A, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065-4896. Phone: 212-746-6313; Fax: 212-746-8816; E-mail: rubinma{at}med.cornell.edu.

Purpose: More than 1,300,000 prostate needle biopsies are done annually in the United States with up to 16% incidence of isolated high-grade prostatic intraepithelial neoplasia (HGPIN). HGPIN has low predictive value for identifying prostate cancer on subsequent needle biopsies in prostate-specific antigen–screened populations. In contemporary series, prostate cancer is detected in 20% of repeat biopsies following a diagnosis of HGPIN. Further, discrete histologic subtypes of HGPIN with clinical implication in management have not been characterized. The TMPRSS2-ERG gene fusion that has recently been described in prostate cancer has also been shown to occur in a subset of HGPIN. This may have significant clinical implications given that TMPRSS2-ERG fusion prostate cancer is associated with a more aggressive clinical course.

Experimental Design: In this study, we assessed a series of HGPIN lesions and paired prostate cancer for the presence of TMPRSS2-ERG gene fusion.

Results: Fusion-positive HGPIN was observed in 16% of the 143 number of lesions, and in all instances, the matching cancer shared the same fusion pattern. Sixty percent of TMPRSS2-ERG fusion prostate cancer had fusion-negative HGPIN.

Conclusions: Given the more aggressive nature of TMPRSS2-ERG prostate cancer, the findings of this study raise the possibility that gene fusion-positive HGPIN lesions are harbingers of more aggressive disease. To date, pathologic, molecular, and clinical variables do not help stratify which men with HGPIN are at increased risk for a cancer diagnosis. Our results suggest that the detection of isolated TMPRSS2-ERG fusion HGPIN would improve the positive predictive value of finding TMPRSS2-ERG fusion prostate cancer in subsequent biopsies.