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[784] Characterization of TMPRSS2-ERG Fusion High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Potential Clinical Implications

JM Mosquera, S Perner, EM Genega, M Sanda, MD Hofer, KD Mertz, PL Paris, J Simko, TA Bismar, G Ayala, RB Shah, M Loda, MA Rubin. Brigham and Womens Hospital, Boston, MA; Harvard Med School, Boston, MA; Beth Israel Deaconess Med Ctr, Boston, MA; Univ of California, San Francisco, CA; McGill Univ, Montreal, QC, Canada; Baylor Col of Medicine, Houston, TX; Univ of Michigan, Ann Arbor, MI

Background: HGPIN has a low predictive value for identifying prostate cancer on subsequent needle biopsies. More than 1,300,000 prostate needle biopsies are performed annually in the United States with an approximate 15% incidence of isolated high-grade prostatic intraepithelial neoplasia. TMPRSS2-ERG fusion has been demonstrated to occur in a subset of HGPIN, and in prostate cancer is associated with higher tumor stage and tumor-specific death or metastasis. We studied HGPIN lesions with paired prostate cancer and correlated TMPRSS2-ERG fusion status.
Design: We assessed 143 HGPIN cases for TMPRSS2-ERG fusion status using FISH. 87% had paired prostate cancer and the remaining 19 cases demonstrated isolated HGPIN without evidence of concurrent cancer. These included two cases of HGPIN with adjacent atypical small acinar proliferation.
Results: Of the 143 HGPIN cases, 16% demonstrated TMPRSS2-ERG gene fusion. All cases shared the same fusion status with the paired prostate cancer. Of 120 TMPRSS2-ERG fusion negative HGPIN cases, 85% had matching adenocarcinoma, and in 32% of these the paired prostate cancer demonstrated TMPRSS2-ERG fusion. Two cases of HGPIN also demonstrated adjacent small atypical glands: one was fusion positive in both areas, whereas the other one showed fusion negative HGPIN with adjacent fusion positive atypical glands. We also identified two cases that showed presence of TMPRSS2-ERG fusion HGPIN and adjacent normal epithelium (with no fusion), within the same gland.
Conclusions: Our results suggest that the detection of isolated TMPRSS2-ERG fusion HGPIN would improve the positive predictive value of finding prostate cancer in subsequent biopsies. Further, TMPRSS2-ERG fusion HGPIN may represent a discrete molecular subtype with clinical implication in management, given the greater risk of predicting aggressive prostate cancer. These findings would also be helpful in clinical trials for chemoprevention of prostate cancer where one of the inclusion criteria is the diagnosis of isolated HGPIN.
Category: Genitourinary (including renal tumors)

Monday, March 3, 2008

Poster # 124, Monday Morning