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.
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-ERGprostate 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.
Authors: Bharathi Laxman; Scott A Tomlins; Rohit Mehra; David S Morris; Lei Wang; Beth E Helgeson; Rajal B Shah; Mark A Rubin; John T Wei; Arul M Chinnaiyan Journal: Neoplasia Date: 2006-10 Impact factor: 5.715
Authors: S M Henshall; D I Quinn; C S Lee; D R Head; D Golovsky; P C Brenner; W Delprado; P D Stricker; J J Grygiel; R L Sutherland Journal: Clin Cancer Res Date: 2001-03 Impact factor: 12.531
Authors: Alan K Meeker; Jessica L Hicks; Elizabeth A Platz; Gerrun E March; Christina J Bennett; Michael J Delannoy; Angelo M De Marzo Journal: Cancer Res Date: 2002-11-15 Impact factor: 12.701
Authors: Sven Perner; Juan-Miguel Mosquera; Francesca Demichelis; Matthias D Hofer; Pamela L Paris; Jeff Simko; Colin Collins; Tarek A Bismar; Arul M Chinnaiyan; Angelo M De Marzo; Mark A Rubin Journal: Am J Surg Pathol Date: 2007-06 Impact factor: 6.394
Authors: G Attard; J Clark; L Ambroisine; G Fisher; G Kovacs; P Flohr; D Berney; C S Foster; A Fletcher; W L Gerald; H Moller; V Reuter; J S De Bono; P Scardino; J Cuzick; C S Cooper Journal: Oncogene Date: 2007-07-16 Impact factor: 9.867
Authors: Andrea Sboner; Francesca Demichelis; Stefano Calza; Yudi Pawitan; Sunita R Setlur; Yujin Hoshida; Sven Perner; Hans-Olov Adami; Katja Fall; Lorelei A Mucci; Philip W Kantoff; Meir Stampfer; Swen-Olof Andersson; Eberhard Varenhorst; Jan-Erik Johansson; Mark B Gerstein; Todd R Golub; Mark A Rubin; Ove Andrén Journal: BMC Med Genomics Date: 2010-03-16 Impact factor: 3.063
Authors: Cindy Ke Zhou; Denise Young; Edward D Yeboah; Sally B Coburn; Yao Tettey; Richard B Biritwum; Andrew A Adjei; Evelyn Tay; Shelley Niwa; Ann Truelove; Judith Welsh; James E Mensah; Robert N Hoover; Isabell A Sesterhenn; Ann W Hsing; Shiv Srivastava; Michael B Cook Journal: Am J Epidemiol Date: 2017-12-15 Impact factor: 4.897
Authors: Sean R Williamson; Shaobo Zhang; Jorge L Yao; Jiaoti Huang; Antonio Lopez-Beltran; Steven Shen; Adeboye O Osunkoya; Gregory T MacLennan; Rodolfo Montironi; Liang Cheng Journal: Mod Pathol Date: 2011-04-15 Impact factor: 7.842
Authors: Xiaoming Ju; Mathew C Casimiro; Michael Gormley; Hui Meng; Xuanmao Jiao; Sanjay Katiyar; Marco Crosariol; Ke Chen; Min Wang; Andrew A Quong; Michael P Lisanti; Adam Ertel; Richard G Pestell Journal: Cancer Res Date: 2013-11-26 Impact factor: 12.701
Authors: Scott A Tomlins; Nallasivam Palanisamy; Javed Siddiqui; Arul M Chinnaiyan; Lakshmi P Kunju Journal: Arch Pathol Lab Med Date: 2012-08 Impact factor: 5.534