PTEN Protein Expression in Transition Zone Prostate Cancer: Loss of Expression and Correlation with TMPRSS2-ERG Rearrangement Status
A Gopalan, C Savage, A Maschino, MA Leversha, J McGuire, HA Al-Ahmadie, SK Tickoo, WL Gerald, VE Reuter, SW Fine. MSKCC, NY, NY
Background: It has been postulated that transition zone prostate cancers (TZ-PC) are distinct from peripheral zone prostate cancers and have more favorable pathologic features and clinical behavior. Molecular differences may contribute to this phenomenon. Loss of PTEN at the genomic and protein levels has been reported to occur in about 30-70% of localized PC and it has been shown that this loss is significantly associated with TMPRSS2-ERG gene rearrangement in human PC. Furthermore, data in mouse models has shown that ERG cooperates with PTEN haploinsufficiency to promote PC progression. PTEN expression and correlation with TMPRSS2-ERG gene rearrangement in TZ-PC has not been previously studied.
Design: 61 TZ-PC arrayed on a TMA in triplicate were evaluated for PTEN expression by immunohistochemistry (mAb clone 6H2.1, 1:50; DAKO). These tumors were also evaluated by interphase FISH for TMPRSS2-ERG gene rearrangement status, using a FISH break-apart probe with BAC clones against 3' ERG and 3' and 5' TMPRSS2.
Results: 17 of 61 (28%) TZ-PC showed complete loss of PTEN protein expression. 16/17 lacked TMPRSS2-ERG gene rearrangement. Only four TZ tumors demonstrated TMPRSS2-ERG rearrangement and 3 of 4 retained at least some PTEN expression. Of the 17 PC with PTEN loss, 15 (88%) and 2 (12%) had Gleason scores of 6 and 7, respectively. No case was associated with a high Gleason score (8-10).
Conclusions: Approximately one quarter of transition zone prostate cancers have loss of PTEN expression at the protein level. Transition zone tumors with PTEN loss were rarely associated with TMPRSS2-ERG gene rearrangement. Correlation of these PTEN and TMPRSS2-ERG findings with well-annotated clinical data may provide further insight into the molecular differences that characterize transition zone prostate cancer.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 132, Wednesday Afternoon