Title | Characterization of TMPRSS2-ERG fusion high-grade prostatic intraepithelial neoplasia and potential clinical implications. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Mosquera J-M, Perner S, Genega EM, Sanda M, Hofer MD, Mertz KD, Paris PL, Simko J, Bismar TA, Ayala G, Shah RB, Loda M, Rubin MA |
Journal | Clin Cancer Res |
Volume | 14 |
Issue | 11 |
Pagination | 3380-5 |
Date Published | 2008 Jun 1 |
ISSN | 1078-0432 |
Keywords | Humans, Male, Middle Aged, Oncogene Proteins, Fusion, Precancerous Conditions, Prostatic Intraepithelial Neoplasia, Prostatic Neoplasms, Tissue Array Analysis |
Abstract | 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 approximately 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. |
DOI | 10.1158/1078-0432.CCR-07-5194 |
Alternate Journal | Clin. Cancer Res. |
PubMed ID | 18519767 |
PubMed Central ID | PMC3717517 |
Grant List | P50 CA089520 / CA / NCI NIH HHS / United States P50 CA090381 / CA / NCI NIH HHS / United States P50 CA090381 / CA / NCI NIH HHS / United States P50CA89520 / CA / NCI NIH HHS / United States R01 AG021404 / AG / NIA NIH HHS / United States R01AG21404 / AG / NIA NIH HHS / United States U01 CA113913 / CA / NCI NIH HHS / United States UO1 CA113913 / CA / NCI NIH HHS / United States |